<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT03029234</url>
  </required_header>
  <id_info>
    <org_study_id>20140242</org_study_id>
    <secondary_id>CFZ005</secondary_id>
    <nct_id>NCT03029234</nct_id>
  </id_info>
  <brief_title>Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed &amp; Refractory Multiple Myeloma</brief_title>
  <official_title>An Open-label, Single-arm, Phase 3 Study of Carfilzomib in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Onyx Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety, tolerability and overall response rate&#xD;
      of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in&#xD;
      China.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 31, 2017</start_date>
  <completion_date type="Actual">June 4, 2021</completion_date>
  <primary_completion_date type="Actual">November 5, 2018</primary_completion_date>
  <phase>Phase 3</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>Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee</measure>
    <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.</time_frame>
    <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator</measure>
    <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.</time_frame>
    <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee</measure>
    <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.</time_frame>
    <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator</measure>
    <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.</time_frame>
    <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee</measure>
    <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 8.9 months.</time_frame>
    <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas is also required</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator</measure>
    <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.</time_frame>
    <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee</measure>
    <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.</time_frame>
    <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator</measure>
    <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.</time_frame>
    <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Overall Response (DOR)</measure>
    <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
    <description>Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.&#xD;
PD:&#xD;
Increase of 25% from lowest response value in any of the following:&#xD;
Serum M-component (absolute increase ≥ 0.5 g/dL) and/or&#xD;
Urine M-component (absolute increase ≥ 200 mg/24 hours)&#xD;
In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase &gt;10 mg/dL)&#xD;
Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas&#xD;
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.&#xD;
DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.&#xD;
DOR was determined based on both investigator and independent review committee response assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Clinical Benefit (DCB)</measure>
    <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
    <description>Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date.&#xD;
Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
    <description>Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy.&#xD;
Progression-free survival was determined based on both investigator and independent review committee response assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From first dose until the data cut-off date of 15 March 2019; median time on follow-up for survival was 15.3 months.</time_frame>
    <description>Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR)</measure>
    <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
    <description>Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) of Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-Life (T½) for Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution (Varea) of Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution at Steady State (Vss) for Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib</measure>
    <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
    <description>MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Relapsed and Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Carfilzomib with Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter).&#xD;
Participants will also receive 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.&#xD;
Participants will receive treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, non-compliance, or intercurrent illness or worsening of a chronic condition, whichever occurs first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.</description>
    <arm_group_label>Carfilzomib with Dexamethasone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.</description>
    <arm_group_label>Carfilzomib with Dexamethasone</arm_group_label>
    <other_name>Kyprolis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: - Multiple myeloma - Subjects must have measurable disease, defined as&#xD;
        one or more of the following: -- Serum M-protein ≥ 1 g/dL -- Urine M-protein ≥ 200 mg/24&#xD;
        hours -- In subjects without measurable serum or urine M-protein, serum free light chain&#xD;
        (SFLC) &gt; 100 mg/L (involved light chain) and an abnormal κ/λ ratio - Subjects must have&#xD;
        been responsive (ie, achieved a minimal response [MR] or better) to at least one of their&#xD;
        prior treatment regimens - Refractory to the most recently received therapy. Refractory&#xD;
        disease defined as ≤ 25% response to, or progressing during therapy or within 60 days after&#xD;
        completion of therapy - Subjects must have received ≥ 2 prior regimens. Induction therapy&#xD;
        and stem cell transplant (± maintenance) will be considered as 1 regimen - Subjects must&#xD;
        have received prior treatment with bortezomib and an immunomodulatory drug - Subjects must&#xD;
        have received an alkylating agent or anthracycline alone or in combination with other&#xD;
        myeloma treatments (this may include high dose melphalan as part of the conditioning&#xD;
        regimen prior to a stem cell transplant) - Males and females ≥ 18 years of age - Life&#xD;
        expectancy of more than 3 months - Eastern Cooperative Oncology Group (ECOG) Performance&#xD;
        Status of 0-2 - Adequate hepatic function, with bilirubin &lt; 2.0 times the upper limit of&#xD;
        normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 3.0&#xD;
        times the ULN - Absolute neutrophil count (ANC) ≥ 1,000/mm³, hemoglobin ≥ 8.0 g/dL, and&#xD;
        platelet count ≥ 50,000/mm³ • Subjects should not have received platelet transfusions for&#xD;
        at least 1 week prior to obtaining the screening platelet count • Screening ANC should be&#xD;
        independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage&#xD;
        colony stimulating factor (GM-CSF) support for ≥ 1 week and pegylated G-CSF for ≥ 2 weeks •&#xD;
        Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per&#xD;
        institutional guidelines is allowed; however, most recent RBC transfusion may not have been&#xD;
        done within 7 days prior to obtaining screening hemoglobin - Calculated or measured&#xD;
        creatinine clearance (CrCl) of ≥ 30 mL/min. Calculated CrCl should be performed by using a&#xD;
        widely accepted equation (eg, the Cockcroft and Gault equation): ([140 - Age] × Mass [kg] /&#xD;
        [72 × Creatinine mg/dL]). Multiply the result by 0.85 if the subject is female. - Left&#xD;
        ventricular ejection fraction (LVEF) ≥ 40%; 2-dimensional transthoracic echocardiogram&#xD;
        (ECHO) is the preferred method of evaluation; multiple gated acquisition scan (MUGA) is&#xD;
        acceptable if ECHO is not available - Written informed consent in accordance with federal,&#xD;
        local, and institutional guidelines - Female subjects of child-bearing potential (FCBP)&#xD;
        must have a negative serum pregnancy test within 21 days prior to enrollment and agree to&#xD;
        use an effective method of contraception during and for 30 days following last dose of&#xD;
        carfilzomib. This protocol defines a FCBP as a sexually mature woman who: 1) has not&#xD;
        undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, or 2) has not&#xD;
        been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any&#xD;
        time in the preceding 24 consecutive months) - Male subjects must use an effective barrier&#xD;
        method of contraception during the study and for 3 months following the last dose of&#xD;
        carfilzomib if sexually active with a FCBP. Male subjects must not donate sperm during&#xD;
        treatment and for an additional 90 days after last dose of carfilzomib. Male subjects with&#xD;
        pregnant partners must practice sexual abstinence or use a condom during vaginal sex.&#xD;
        Exclusion Criteria: - Waldenström's macroglobulinemia or immunoglobulin M (IgM) multiple&#xD;
        myeloma - Subjects who failed to achieve at least a confirmed MR on any of their prior&#xD;
        regimens - Subjects with non-secretory multiple myeloma, defined as &lt; 1 g/dL M-protein in&#xD;
        serum and &lt; 200 mg/24 hour M-protein in urine and SFLC ≤ 100 mg/L (involved light chain) -&#xD;
        Glucocorticoid therapy (prednisone &gt; 10 mg/day or equivalent) within 3 weeks prior to Cycle&#xD;
        1 Day 1 - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,&#xD;
        and skin changes) - Plasma cell leukemia (&gt; 2.0 × 10⁹/L circulating plasma cells by&#xD;
        standard differential) - Chemotherapy with approved or investigative anticancer&#xD;
        therapeutics including steroid therapy within the 3 weeks prior to Cycle 1 Day 1 -&#xD;
        Radiation therapy or immunotherapy in the 4 weeks prior to Cycle 1 Day 1; localized&#xD;
        radiation therapy within 1 week prior to Cycle 1 Day 1 - Participation in an&#xD;
        investigational therapeutic study within 3 weeks or within 5 drug half-lives (T½) prior to&#xD;
        Cycle 1 Day 1, whichever time is greater - Prior treatment with carfilzomib - Major surgery&#xD;
        within 3 weeks before Cycle 1 Day 1 - Congestive heart failure (CHF; New York Heart&#xD;
        Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled&#xD;
        by conventional intervention, or myocardial infarction within 6 months - Uncontrolled&#xD;
        hypertension (a sustained systolic blood pressure &gt; 140 mmHg and/or diastolic blood&#xD;
        pressure &gt; 90 mmHg) - Acute active infection requiring systemic antibiotics, antivirals, or&#xD;
        antifungals within 2 weeks prior to Cycle 1 Day 1 - Known human immunodeficiency virus&#xD;
        (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with&#xD;
        hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy&#xD;
        directed at hepatitis B: these patients are allowed) - Non-hematologic malignancy within&#xD;
        the past 3 years except: -- Adequately treated basal cell or squamous cell skin cancer, --&#xD;
        Carcinoma in situ of the cervix, or -- Prostate cancer &lt; Gleason Score 6 with stable&#xD;
        prostate-specific antigen - Subjects with treatment-related myelodysplastic syndrome -&#xD;
        Significant neuropathy (Grade 3, 4, or Grade 2 with pain) at the time of baseline&#xD;
        evaluation - Subjects in whom the required program of fluid hydration is contraindicated,&#xD;
        eg, due to pre-existing pulmonary, cardiac, or renal impairment - Subjects with known or&#xD;
        suspected amyloidosis - Subjects with pleural effusions requiring thoracentesis - Subjects&#xD;
        with ascites requiring paracentesis - Any clinically significant medical disease or&#xD;
        condition, that in the investigator's opinion, may interfere with protocol adherence or a&#xD;
        subject's ability to give informed consent - Female subjects who are pregnant or lactating,&#xD;
        or planning to become pregnant during treatment and for an additional 30 days after&#xD;
        discontinuing carfilzomib. - Serious psychiatric or medical conditions that could interfere&#xD;
        with treatment&#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>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Chao Yang Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University Third Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100191</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fujian Medical University Union Hospital</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yat-Sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guangzhou First Peoples Hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510180</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450008</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Central Hospital of Wuhan</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Soochow University</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <zip>215004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of China Medical University</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital, Sichuang University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University General Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital, College of Medicine, Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Changzheng Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <reference>
    <citation>Du J, Fang B, Li J, Jin J, Wang S, Zou D, Cai Z, Wang H, Hu J, Li W, Fu C, Shao Z, Xia Z, Liu P, Niu T, Tang ET, Kimball AS, Hou J, Chen W. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021 Mar;113(3):422-429. doi: 10.1007/s12185-020-03044-z. Epub 2021 Jan 3.</citation>
    <PMID>33389656</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>November 4, 2019</results_first_submitted>
  <results_first_submitted_qc>November 4, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 21, 2019</results_first_posted>
  <last_update_submitted>May 4, 2022</last_update_submitted>
  <last_update_submitted_qc>May 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.</ipd_access_criteria>
    <ipd_url>https://www.amgen.com/datasharing</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03029234/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 31, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03029234/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 18 centers in China. The primary efficacy analysis was prespecified to occur when all enrolled participants had received 6 cycles of therapy or discontinued treatment. This occurred on November 5, 2018. A final analysis for efficacy was prespecified when all enrolled participants had the opportunity to be treated with at least 12 cycles. This occurred on March 15, 2019.&#xD;
The final analysis for safety occurred once all participants completed the study, 4 June 2021.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Carfilzomib With Dexamethasone</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Carfilzomib</title>
              <participants_list>
                <participants group_id="P1" count="123"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="99"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="91"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety population consisted of all enrolled participants who received at least 1 dose of carfilzomib.</population>
      <group_list>
        <group group_id="B1">
          <title>Carfilzomib With Dexamethasone</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="123"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="123"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.8" spread="9.4"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="123"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="123"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="123"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about &gt; 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair &gt; 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="123"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>0 (Fully active)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1 (Restricted but ambulatory)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2 (Ambulatory but unable to work)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time From Initial Diagnosis to First Dose</title>
          <description>One participant had a data entry error with year of diagnosis entered as 2017 instead of 2014, leading to an erroneous minimum time since diagnosis reported.</description>
          <population>Participants with available data</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.70" lower_limit="0.4" upper_limit="182.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total Number of Prior Regimens</title>
          <units>regimens</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="123"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.0" lower_limit="2" upper_limit="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee</title>
        <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
        <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee</title>
          <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.8" lower_limit="27.3" upper_limit="44.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The prespecified threshold that the primary endpoint would be met was if the lower limit of the 95% confidence interval (CI) was greater than 18%.</non_inferiority_desc>
            <param_type>Overall response rate</param_type>
            <param_value>35.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>27.3</ci_lower_limit>
            <ci_upper_limit>44.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator</title>
        <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
        <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator</title>
          <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0" lower_limit="26.6" upper_limit="44.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee</title>
        <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
        <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee</title>
          <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.8" lower_limit="27.3" upper_limit="44.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator</title>
        <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
        <time_frame>Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator</title>
          <description>ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.&#xD;
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt; 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein &lt;100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).&#xD;
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to &lt; 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0" lower_limit="26.6" upper_limit="44.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee</title>
        <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas is also required</description>
        <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 8.9 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee</title>
          <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas is also required</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.0" lower_limit="38.9" upper_limit="57.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator</title>
        <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
        <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator</title>
          <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.3" lower_limit="37.3" upper_limit="55.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee</title>
        <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
        <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee</title>
          <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.0" lower_limit="38.9" upper_limit="57.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator</title>
        <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
        <time_frame>Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator</title>
          <description>Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).&#xD;
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a &gt;50% reduction in the size of soft tissue plasmacytomas was also required.</description>
          <population>Safety population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.3" lower_limit="37.3" upper_limit="55.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Overall Response (DOR)</title>
        <description>Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.&#xD;
PD:&#xD;
Increase of 25% from lowest response value in any of the following:&#xD;
Serum M-component (absolute increase ≥ 0.5 g/dL) and/or&#xD;
Urine M-component (absolute increase ≥ 200 mg/24 hours)&#xD;
In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase &gt;10 mg/dL)&#xD;
Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas&#xD;
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.&#xD;
DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.&#xD;
DOR was determined based on both investigator and independent review committee response assessments.</description>
        <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
        <population>Safety population participants who achieved an overall response (best response of PR or better)</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Overall Response (DOR)</title>
          <description>Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.&#xD;
PD:&#xD;
Increase of 25% from lowest response value in any of the following:&#xD;
Serum M-component (absolute increase ≥ 0.5 g/dL) and/or&#xD;
Urine M-component (absolute increase ≥ 200 mg/24 hours)&#xD;
In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase &gt;10 mg/dL)&#xD;
Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas&#xD;
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.&#xD;
DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.&#xD;
DOR was determined based on both investigator and independent review committee response assessments.</description>
          <population>Safety population participants who achieved an overall response (best response of PR or better)</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Independent Review Committee Assessment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.2" lower_limit="7.4" upper_limit="NA">Could not be estimated due to the low number of events at the analysis cut-off date</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigator Assessment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.7" lower_limit="7.4" upper_limit="NA">Could not be estimated due to the low number of events at the analysis cut-off date</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Clinical Benefit (DCB)</title>
        <description>Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date.&#xD;
Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.</description>
        <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
        <population>Safety population participants who achieved a best overall response of minimal response or better.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Clinical Benefit (DCB)</title>
          <description>Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date.&#xD;
Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.</description>
          <population>Safety population participants who achieved a best overall response of minimal response or better.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Independent Review Committee Assessment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" lower_limit="7.3" upper_limit="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigator Assessment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="57"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" lower_limit="7.4" upper_limit="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy.&#xD;
Progression-free survival was determined based on both investigator and independent review committee response assessments.</description>
        <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy.&#xD;
Progression-free survival was determined based on both investigator and independent review committee response assessments.</description>
          <population>Safety population</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Independent Review Committee Assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" lower_limit="4.6" upper_limit="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigator Assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" lower_limit="4.6" upper_limit="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).</description>
        <time_frame>From first dose until the data cut-off date of 15 March 2019; median time on follow-up for survival was 15.3 months.</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).</description>
          <population>Safety population</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.2" lower_limit="11.5" upper_limit="NA">Could not be estimated due to the low number of events at the time of the analysis.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Response (TTR)</title>
        <description>Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.</description>
        <time_frame>Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.</time_frame>
        <population>Safety population participants who achieved an overall response (best response of PR or better)</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Response (TTR)</title>
          <description>Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.</description>
          <population>Safety population participants who achieved an overall response (best response of PR or better)</population>
          <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="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Independent Review Committee Assessment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigator Assessment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of Carfilzomib</title>
        <description>Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of Carfilzomib</title>
          <description>Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.</description>
          <population>Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="744" spread="326"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1210" spread="678"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) of Carfilzomib</title>
        <description>Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) of Carfilzomib</title>
          <description>Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.</description>
          <population>Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.50" lower_limit="0.083" upper_limit="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.50" lower_limit="0.083" upper_limit="0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib</title>
        <description>AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib</title>
          <description>AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.</description>
          <population>Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.</population>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="254" spread="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="401" spread="173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib</title>
        <description>AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib</title>
          <description>AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.</description>
          <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="256" spread="104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="401" spread="173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Half-Life (T½) for Carfilzomib</title>
        <description>The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-Life (T½) for Carfilzomib</title>
          <description>The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.</description>
          <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.651" spread="0.259"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.792" spread="0.281"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion</title>
        <description>Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion</title>
          <description>Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.</description>
          <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="157" spread="61.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153" spread="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution (Varea) of Carfilzomib</title>
        <description>Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution (Varea) of Carfilzomib</title>
          <description>Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.</description>
          <population>Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) &lt; 0.8 or percent extrapolated AUC &gt; 20% were excluded from the analysis.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148" spread="88.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="164" spread="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution at Steady State (Vss) for Carfilzomib</title>
        <description>Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>PK analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination &lt; 0.8, percent extrapolated AUC &gt; 20%, or negative values for Vss were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution at Steady State (Vss) for Carfilzomib</title>
          <description>Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.</description>
          <population>PK analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination &lt; 0.8, percent extrapolated AUC &gt; 20%, or negative values for Vss were excluded from the analysis.</population>
          <units>liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0" spread="20.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.2" spread="17.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib</title>
        <description>MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.</description>
        <time_frame>Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.</time_frame>
        <population>PK analyses were conducted on a subset of participants at selected sites. Results are reported for the participants in PK analysis population with available data at each time point. PK profiles with a coefficient of determination &lt; 0.8, percent extrapolated AUC &gt; 20%, or negative values for MRT were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib With Dexamethasone</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib</title>
          <description>MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.</description>
          <population>PK analyses were conducted on a subset of participants at selected sites. Results are reported for the participants in PK analysis population with available data at each time point. PK profiles with a coefficient of determination &lt; 0.8, percent extrapolated AUC &gt; 20%, or negative values for MRT were excluded from the analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 (20 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.225" spread="0.0856"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 (27 mg/m²)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.196" spread="0.0975"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks.</time_frame>
      <desc>All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Carfilzomib With Dexamethasone</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.&#xD;
Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="91" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="68" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac amyloidosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchiolitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Escherichia sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Plasma cell myeloma</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Lipoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Myelopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Nerve compression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Obstructive airways disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Organising pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="123" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="76" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="60" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Bilirubin conjugated increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood phosphorus increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Lymphocyte percentage decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Mean cell volume increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Neutrophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Neutrophil percentage increased</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="60" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Prealbumin decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypoproteinaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="123"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="123"/>
              </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>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.com</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/NCT03029234
org study id: 20140242
secondary id: CFZ005
nct id: NCT03029234
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate the safety, tolerability and overall response rate
      of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in
      China.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee
time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.
description: ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.
measure: Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator
time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.
description: ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.
measure: Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee
time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.
description: ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.
measure: Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator
time frame: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.
description: ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.
sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).
PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.
measure: Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee
time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 8.9 months.
description: Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required
measure: Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator
time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.
description: Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.
measure: Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee
time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.
description: Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.
measure: Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator
time frame: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 13.1 months.
description: Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).
MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.
measure: Duration of Overall Response (DOR)
time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
description: Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.
PD:
Increase of 25% from lowest response value in any of the following:
Serum M-component (absolute increase ≥ 0.5 g/dL) and/or
Urine M-component (absolute increase ≥ 200 mg/24 hours)
In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL)
Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.
DOR was determined based on both investigator and independent review committee response assessments.
measure: Duration of Clinical Benefit (DCB)
time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
description: Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date.
Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.
measure: Progression-free Survival (PFS)
time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
description: Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy.
Progression-free survival was determined based on both investigator and independent review committee response assessments.
measure: Overall Survival (OS)
time frame: From first dose until the data cut-off date of 15 March 2019; median time on follow-up for survival was 15.3 months.
description: Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).
measure: Time to Response (TTR)
time frame: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.
description: Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.
measure: Maximum Observed Plasma Concentration (Cmax) of Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.
measure: Time to Maximum Plasma Concentration (Tmax) of Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.
measure: Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.
measure: Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.
measure: Terminal Elimination Half-Life (T½) for Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.
measure: Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.
measure: Volume of Distribution (Varea) of Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.
measure: Volume of Distribution at Steady State (Vss) for Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.
measure: Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib
time frame: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.
description: MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.
arm group label: Carfilzomib with Dexamethasone
arm group type: Experimental
description: Participants will receive carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter).
Participants will also receive 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.
Participants will receive treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, non-compliance, or intercurrent illness or worsening of a chronic condition, whichever occurs first.
intervention type: Drug
intervention name: Dexamethasone
description: 20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.
arm group label: Carfilzomib with Dexamethasone
intervention type: Drug
intervention name: Carfilzomib
description: Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.
arm group label: Carfilzomib with Dexamethasone
other name: Kyprolis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
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country: China
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
citation: Du J, Fang B, Li J, Jin J, Wang S, Zou D, Cai Z, Wang H, Hu J, Li W, Fu C, Shao Z, Xia Z, Liu P, Niu T, Tang ET, Kimball AS, Hou J, Chen W. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021 Mar;113(3):422-429. doi: 10.1007/s12185-020-03044-z. Epub 2021 Jan 3.
PMID: 33389656
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
ipd url: https://www.amgen.com/datasharing
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