<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03256045</url>
  </required_header>
  <id_info>
    <org_study_id>9757</org_study_id>
    <secondary_id>NCI-2017-00453</secondary_id>
    <secondary_id>9757</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG1016013</secondary_id>
    <nct_id>NCT03256045</nct_id>
  </id_info>
  <brief_title>Panobinostat, Carfilzomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>CLBH589DUS108T: Panobinostat With Carfilzomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Correlation With In Vitro Chemosensitivity Testing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>SecuraBio</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well panobinostat, carfilzomib, and dexamethasone work in&#xD;
      treating patients with multiple myeloma that has come back (relapsed) or does not respond to&#xD;
      treatment (refractory). Panobinostat may stop the growth of cancer cells by blocking some of&#xD;
      the enzymes needed for cell growth. Chemotherapy drugs, such as carfilzomib and&#xD;
      dexamethasone, work in different ways to stop the growth of cancer cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. Using multiple&#xD;
      myeloma cells from patients' blood samples, the researchers will do laboratory tests to look&#xD;
      at how well each of the drugs, alone and in different combinations, kill multiple myeloma&#xD;
      cells. If the laboratory tests work well, they may be used in the future to help plan&#xD;
      treatment for future patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To correlate in vitro drug sensitivity testing with clinical response by determining the&#xD;
      rate of in vitro drug sensitivity to panobinostat, carfilzomib, and dexamethasone singly and&#xD;
      in combination, doublets and triplets.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To monitor response rates (partial response [PR], very good partial response [VGPR], and&#xD;
      complete response) using the International Myeloma Working Group Uniform Response Criteria&#xD;
      for Multiple Myeloma.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. Progression free survival and overall survival will be assessed for up to 3 years after&#xD;
      last dose.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive panobinostat orally (PO) on days 1, 3, 5, 15, 17, and 19. Patients also&#xD;
      receive carfilzomib intravenously (IV) and dexamethasone PO on days 1, 2, 8, 9, 15, and 16.&#xD;
      Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or&#xD;
      unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples&#xD;
      for testing via in vitro chemosensitivity assay.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for up to 3&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated due to loss of funding and former PI left the institution&#xD;
  </why_stopped>
  <start_date type="Actual">February 8, 2018</start_date>
  <completion_date type="Actual">February 5, 2021</completion_date>
  <primary_completion_date type="Actual">February 5, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Overall Response, by Subject</measure>
    <time_frame>14 months</time_frame>
    <description>Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject</measure>
    <time_frame>At baseline</time_frame>
    <description>Multiple myeloma cells are added to assay with panobinostat. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-9.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject</measure>
    <time_frame>At baseline</time_frame>
    <description>Multiple myeloma cells are added to assay with carfilzomib. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject</measure>
    <time_frame>At baseline</time_frame>
    <description>Multiple myeloma cells are added to assay with dexamethasone. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-6.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.</measure>
    <time_frame>At baseline</time_frame>
    <description>Concentration of carfilzomib and panobinostat in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI&lt;1 synergy; CI&gt;1 antagonism.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Synergy of Panobinostat and Dexamethasone in Combination, Per Subject</measure>
    <time_frame>At baseline</time_frame>
    <description>Concentration of panobinostat and dexamethasone in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI&lt;1 synergy; CI&gt;1 antagonism.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Refractory Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19. Patients also receive carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay</arm_group_label>
    <other_name>Kyprolis</other_name>
    <other_name>PR-171</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Chemosensitivity Assay</intervention_name>
    <description>Undergo in vitro chemosensitivity testing</description>
    <arm_group_label>Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay</arm_group_label>
    <other_name>Chemosensitivity Testing</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay</arm_group_label>
    <other_name>Aacidexam</other_name>
    <other_name>Adexone</other_name>
    <other_name>Aknichthol Dexa</other_name>
    <other_name>Alba-Dex</other_name>
    <other_name>Alin</other_name>
    <other_name>Alin Depot</other_name>
    <other_name>Alin Oftalmico</other_name>
    <other_name>Amplidermis</other_name>
    <other_name>Anemul mono</other_name>
    <other_name>Auricularum</other_name>
    <other_name>Auxiloson</other_name>
    <other_name>Baycuten</other_name>
    <other_name>Baycuten N</other_name>
    <other_name>Cortidexason</other_name>
    <other_name>Cortisumman</other_name>
    <other_name>Decacort</other_name>
    <other_name>Decadrol</other_name>
    <other_name>Decadron</other_name>
    <other_name>Decalix</other_name>
    <other_name>Decameth</other_name>
    <other_name>Decasone R.p.</other_name>
    <other_name>Dectancyl</other_name>
    <other_name>Dekacort</other_name>
    <other_name>Deltafluorene</other_name>
    <other_name>Deronil</other_name>
    <other_name>Desamethasone</other_name>
    <other_name>Desameton</other_name>
    <other_name>Dexa-Mamallet</other_name>
    <other_name>Dexa-Rhinosan</other_name>
    <other_name>Dexa-Scheroson</other_name>
    <other_name>Dexa-sine</other_name>
    <other_name>Dexacortal</other_name>
    <other_name>Dexacortin</other_name>
    <other_name>Dexafarma</other_name>
    <other_name>Dexafluorene</other_name>
    <other_name>Dexalocal</other_name>
    <other_name>Dexamecortin</other_name>
    <other_name>Dexameth</other_name>
    <other_name>Dexamethasonum</other_name>
    <other_name>Dexamonozon</other_name>
    <other_name>Dexapos</other_name>
    <other_name>Dexinoral</other_name>
    <other_name>Dexone</other_name>
    <other_name>Dinormon</other_name>
    <other_name>Fluorodelta</other_name>
    <other_name>Fortecortin</other_name>
    <other_name>Gammacorten</other_name>
    <other_name>Hexadecadrol</other_name>
    <other_name>Hexadrol</other_name>
    <other_name>Lokalison-F</other_name>
    <other_name>Loverine</other_name>
    <other_name>Methylfluorprednisolone</other_name>
    <other_name>Millicorten</other_name>
    <other_name>Mymethasone</other_name>
    <other_name>Orgadrone</other_name>
    <other_name>Spersadex</other_name>
    <other_name>Visumetazone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Panobinostat</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay</arm_group_label>
    <other_name>Faridak</other_name>
    <other_name>Farydak</other_name>
    <other_name>LBH589</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of multiple myeloma refractory to or relapsed after &gt;= 1 line of prior&#xD;
             therapy (International Myeloma Working Group [IMWG] criteria)&#xD;
&#xD;
          -  Measurable disease, as indicated by one of the following:&#xD;
&#xD;
               -  Serum monoclonal (M)-protein &gt;= 1.0 g/dL&#xD;
&#xD;
               -  Elevated involved free light chain &gt;= 10 mg/dL as per IMWG criteria, and abnormal&#xD;
                  ratio&#xD;
&#xD;
               -  Urine Bence Jones protein &gt; 200 mg/24 hour (hr)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 750/uL&#xD;
&#xD;
          -  Platelet count &gt;= 75,000/uL&#xD;
&#xD;
          -  Hemoglobin &gt;= 7 g/dL&#xD;
&#xD;
          -  Creatinine =&lt; 2.0 mg/dL or calculated creatinine clearance &gt;= 30 mL/min&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN) unless elevation is thought to be&#xD;
             due to Gilbert's syndrome&#xD;
&#xD;
          -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and&#xD;
             serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =&lt; 2.5 x&#xD;
             ULN&#xD;
&#xD;
          -  Patients must avoid consumption of grapefruit, pomegranates, starfruit, Seville&#xD;
             oranges or products containing the juice of each during the entire study and&#xD;
             preferably 7 days before the first dose of study medications; orange juice is allowed&#xD;
&#xD;
          -  Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, should have a pregnancy test prior to the initiation of treatment&#xD;
             and use highly effective methods of contraception during and for 3 months post study&#xD;
             treatment; highly effective contraception methods include total abstinence, female&#xD;
             sterilization, male sterilization, use of oral, injected, or implanted hormonal&#xD;
             methods of contraception or placement of an intrauterine device (IUD) or intrauterine&#xD;
             system (IUS) or other forms of hormonal contraception that have comparable efficacy;&#xD;
             women using hormonal contraceptives should additionally use a barrier method of&#xD;
             contraception; women are considered post-menopausal and not of child-bearing potential&#xD;
             if they have had 12 months of natural amenorrhea or have had surgical bilateral&#xD;
             oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at&#xD;
             least 6 weeks ago&#xD;
&#xD;
          -  Sexually active males must use a condom during intercourse while taking study drug and&#xD;
             for 6 months after stopping treatment; males should not father a child in this period;&#xD;
             a condom is required to be used also by vasectomized men as well as during intercourse&#xD;
             with a male partner; female partners of sexually active men should also use an&#xD;
             effective contraception during treatment and for 6 months after their male partner has&#xD;
             stopped taking the drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Another bone marrow malignancy&#xD;
&#xD;
          -  Another cancer with expected survival of &lt; 2 years&#xD;
&#xD;
          -  Active viral, bacterial, or fungal infection progressing on current treatment&#xD;
&#xD;
          -  Clinically significant uncontrolled heart disease and/or recent cardiac event within 6&#xD;
             months prior to enrollment, such as:&#xD;
&#xD;
               -  History of angina pectoris, symptomatic pericarditis, or myocardial infarction&#xD;
&#xD;
               -  Left ventricular ejection fraction (LVEF) &lt; 45% as determined by echocardiogram&#xD;
                  (ECHO) or multi gated acquisition (MUGA) scan&#xD;
&#xD;
               -  History or presence of any significant, uncontrolled, or persistent cardiac&#xD;
                  arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias or conduction&#xD;
                  abnormality; stable atrial fibrillation within 6 months prior to randomization is&#xD;
                  permitted&#xD;
&#xD;
               -  Presence of unstable atrial fibrillation (ventricular response rate &gt; 100 beats&#xD;
                  per minute [bpm]); NOTE: patients with stable atrial fibrillation can be enrolled&#xD;
                  provided they do not meet other cardiac exclusion criteria&#xD;
&#xD;
               -  Resting heart rate &lt; 50 bpm&#xD;
&#xD;
               -  Complete left bundle branch block (LBBB), bifascicular block&#xD;
&#xD;
               -  Congenital long QT syndrome&#xD;
&#xD;
               -  Any clinically significant ST segment and/or T-wave abnormalities&#xD;
&#xD;
               -  Corrected QT (QTcF) &gt; 450 msec for males and &gt; 470 msec for females using&#xD;
                  Fridericia's correction on screening electrocardiogram (ECG)&#xD;
&#xD;
               -  History of documented congestive heart failure (New York Heart Association&#xD;
                  functional classification III-IV)&#xD;
&#xD;
               -  Uncontrolled hypertension defined by a systolic blood pressure (SBP) &gt;= 150 mmHg&#xD;
                  and/or diastolic blood pressure (DBP) &gt;= 100 mmHg with or without&#xD;
                  antihypertensive medication; NOTE: initiation or adjustment of antihypertensive&#xD;
                  medication(s) is allowed prior to screening&#xD;
&#xD;
               -  Other clinically significant heart disease or vascular disease&#xD;
&#xD;
          -  Currently taking medications that have known or definite risk of prolonging the QT&#xD;
             interval or inducing Torsades de pointes (TdP); the medication must be discontinued or&#xD;
             switched to a safe alternative medication prior to starting treatment; specific&#xD;
             exception is allowed for patients on long-standing medications that have risk of&#xD;
             prolonging QT interval or inducing TdP if screening ECG does not indicate a prolonged&#xD;
             QT abnormality&#xD;
&#xD;
          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
             alter the absorption of panobinostat or dexamethasone (e.g. ulcerative disease&#xD;
             uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or&#xD;
             small bowel resection)&#xD;
&#xD;
          -  Unresolved diarrhea &gt;= Common Terminology Criteria for Adverse Events (CTCAE) grade 2&#xD;
             or a medical condition associated with chronic diarrhea (such as irritable bowel&#xD;
             syndrome, inflammatory bowel disease)&#xD;
&#xD;
          -  Major surgery =&lt; 14 days prior to starting study treatment or side effects of surgery&#xD;
             that have not recovered to &lt; CTCAE grade 2&#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>Andrew Cowan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <results_first_submitted>February 1, 2022</results_first_submitted>
  <results_first_submitted_qc>May 6, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 9, 2022</results_first_posted>
  <last_update_submitted>May 6, 2022</last_update_submitted>
  <last_update_submitted_qc>May 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Andrew Cowan</investigator_full_name>
    <investigator_title>Assistant Professor, Division of Medical Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Panobinostat</mesh_term>
    <mesh_term>Ichthammol</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 22, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT03256045/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
          <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
          <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67" lower_limit="49" upper_limit="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior therapy regimes</title>
          <units>number of regimens</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5" lower_limit="2" upper_limit="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior autologous transplant</title>
          <units>percentage of participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="88.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Revised ISS Stage</title>
          <description>Revised ISS is the Revised International Staging System, which is used to stage multiple myeloma at diagnosis. It takes into account a patient's albumin, beta-2-microglobulin, lactate dehydrogenase levels, and chromosomal abnormalities detected by FISH to predict survival. There are three stages: I, II, and III. The lower the stage, the longer the progression-free survival.</description>
          <units>ISS Stage</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.5" lower_limit="1" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Overall Response, by Subject</title>
        <description>Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.</description>
        <time_frame>14 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
            <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response, by Subject</title>
          <description>Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.</description>
          <units>IMWG Uniform Response Grade</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject MM-82</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-92</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-95</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-98</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-99</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-109</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject M-111</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject</title>
        <description>Multiple myeloma cells are added to assay with panobinostat. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-9.</description>
        <time_frame>At baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
            <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject</title>
          <description>Multiple myeloma cells are added to assay with panobinostat. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-9.</description>
          <units>nM</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject MM-82</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-92</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-95</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-98</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-99</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-109</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-111</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject</title>
        <description>Multiple myeloma cells are added to assay with carfilzomib. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells.</description>
        <time_frame>At baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
            <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject</title>
          <description>Multiple myeloma cells are added to assay with carfilzomib. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells.</description>
          <units>nM</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject MM-82</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.479"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-92</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-95</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.269"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0048"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-98</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-99</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-109</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-111</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject</title>
        <description>Multiple myeloma cells are added to assay with dexamethasone. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-6.</description>
        <time_frame>At baseline</time_frame>
        <population>Results for subject MM-92 were not reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
            <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject</title>
          <description>Multiple myeloma cells are added to assay with dexamethasone. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-6.</description>
          <population>Results for subject MM-92 were not reported.</population>
          <units>uM</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject MM-82</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-95</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-98</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-99</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-109</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-111</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.</title>
        <description>Concentration of carfilzomib and panobinostat in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI&lt;1 synergy; CI&gt;1 antagonism.</description>
        <time_frame>At baseline</time_frame>
        <population>CI score was not reported for subject MM-82.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
            <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.</title>
          <description>Concentration of carfilzomib and panobinostat in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI&lt;1 synergy; CI&gt;1 antagonism.</description>
          <population>CI score was not reported for subject MM-82.</population>
          <units>Combination index</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject MM-91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-92</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-95</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-98</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-99</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-109</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-111</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Synergy of Panobinostat and Dexamethasone in Combination, Per Subject</title>
        <description>Concentration of panobinostat and dexamethasone in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI&lt;1 synergy; CI&gt;1 antagonism.</description>
        <time_frame>At baseline</time_frame>
        <population>CI score was not reported for subject MM-82</population>
        <group_list>
          <group group_id="O1">
            <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
            <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Synergy of Panobinostat and Dexamethasone in Combination, Per Subject</title>
          <description>Concentration of panobinostat and dexamethasone in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI&lt;1 synergy; CI&gt;1 antagonism.</description>
          <population>CI score was not reported for subject MM-82</population>
          <units>CI score</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject MM-91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-92</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-95</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-96</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-98</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-99</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-109</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject MM-111</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.</time_frame>
      <desc>Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.</desc>
      <group_list>
        <group group_id="E1">
          <title>Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone</title>
          <description>Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Non-ST segment elevation myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fracture, pathologic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fracture, non-pathologic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Study was limited by lower accrual than expected due to: competing studies, other investigators' treatment preferences, and ultimately, the departure of the initial PI from the institution. Because of PI's departure and lab closure, the study closed to accrual after the 9th patient enrolled. Because only 9 subjects were enrolled and some in-vitro assay results are unavailable, it is difficult to analyze the in-vitro assay results and determine the parameters that predict disease response.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Andrew Cowan</name_or_title>
      <organization>University of Washington</organization>
      <phone>206-606-7348</phone>
      <email>ajcowan@seattlecca.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03256045
org study id: 9757
secondary id: NCI-2017-00453
secondary id: 9757
secondary id: P30CA015704
secondary id: RG1016013
nct id: NCT03256045
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well panobinostat, carfilzomib, and dexamethasone work in
      treating patients with multiple myeloma that has come back (relapsed) or does not respond to
      treatment (refractory). Panobinostat may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Chemotherapy drugs, such as carfilzomib and
      dexamethasone, work in different ways to stop the growth of cancer cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Using multiple
      myeloma cells from patients' blood samples, the researchers will do laboratory tests to look
      at how well each of the drugs, alone and in different combinations, kill multiple myeloma
      cells. If the laboratory tests work well, they may be used in the future to help plan
      treatment for future patients.
PRIMARY OBJECTIVE:

      I. To correlate in vitro drug sensitivity testing with clinical response by determining the
      rate of in vitro drug sensitivity to panobinostat, carfilzomib, and dexamethasone singly and
      in combination, doublets and triplets.

      SECONDARY OBJECTIVE:

      I. To monitor response rates (partial response [PR], very good partial response [VGPR], and
      complete response) using the International Myeloma Working Group Uniform Response Criteria
      for Multiple Myeloma.

      EXPLORATORY OBJECTIVE:

      I. Progression free survival and overall survival will be assessed for up to 3 years after
      last dose.

      OUTLINE:

      Patients receive panobinostat orally (PO) on days 1, 3, 5, 15, 17, and 19. Patients also
      receive carfilzomib intravenously (IV) and dexamethasone PO on days 1, 2, 8, 9, 15, and 16.
      Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or
      unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples
      for testing via in vitro chemosensitivity assay.

      After completion of study treatment, patients are followed up every 3 months for up to 3
      years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Overall Response, by Subject
time frame: 14 months
description: Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.
measure: Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
time frame: At baseline
description: Multiple myeloma cells are added to assay with panobinostat. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-9.
measure: Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
time frame: At baseline
description: Multiple myeloma cells are added to assay with carfilzomib. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells.
measure: Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
time frame: At baseline
description: Multiple myeloma cells are added to assay with dexamethasone. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-6.
measure: Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
time frame: At baseline
description: Concentration of carfilzomib and panobinostat in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI<1 synergy; CI>1 antagonism.
measure: Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
time frame: At baseline
description: Concentration of panobinostat and dexamethasone in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI<1 synergy; CI>1 antagonism.
arm group label: Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
arm group type: Experimental
description: Patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19. Patients also receive carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay.
intervention type: Drug
intervention name: Carfilzomib
description: Given IV
arm group label: Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
other name: Kyprolis
other name: PR-171
intervention type: Other
intervention name: Chemosensitivity Assay
description: Undergo in vitro chemosensitivity testing
arm group label: Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
other name: Chemosensitivity Testing
intervention type: Drug
intervention name: Dexamethasone
description: Given PO
arm group label: Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
other name: Aacidexam
other name: Adexone
other name: Aknichthol Dexa
other name: Alba-Dex
other name: Alin
other name: Alin Depot
other name: Alin Oftalmico
other name: Amplidermis
other name: Anemul mono
other name: Auricularum
other name: Auxiloson
other name: Baycuten
other name: Baycuten N
other name: Cortidexason
other name: Cortisumman
other name: Decacort
other name: Decadrol
other name: Decadron
other name: Decalix
other name: Decameth
other name: Decasone R.p.
other name: Dectancyl
other name: Dekacort
other name: Deltafluorene
other name: Deronil
other name: Desamethasone
other name: Desameton
other name: Dexa-Mamallet
other name: Dexa-Rhinosan
other name: Dexa-Scheroson
other name: Dexa-sine
other name: Dexacortal
other name: Dexacortin
other name: Dexafarma
other name: Dexafluorene
other name: Dexalocal
other name: Dexamecortin
other name: Dexameth
other name: Dexamethasonum
other name: Dexamonozon
other name: Dexapos
other name: Dexinoral
other name: Dexone
other name: Dinormon
other name: Fluorodelta
other name: Fortecortin
other name: Gammacorten
other name: Hexadecadrol
other name: Hexadrol
other name: Lokalison-F
other name: Loverine
other name: Methylfluorprednisolone
other name: Millicorten
other name: Mymethasone
other name: Orgadrone
other name: Spersadex
other name: Visumetazone
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
intervention type: Drug
intervention name: Panobinostat
description: Given PO
arm group label: Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
other name: Faridak
other name: Farydak
other name: LBH589
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Cowan
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Andrew Cowan
investigator title: Assistant Professor, Division of Medical Oncology
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Panobinostat
mesh term: Ichthammol
mesh term: BB 1101
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was limited by lower accrual than expected due to: competing studies, other investigators' treatment preferences, and ultimately, the departure of the initial PI from the institution. Because of PI's departure and lab closure, the study closed to accrual after the 9th patient enrolled. Because only 9 subjects were enrolled and some in-vitro assay results are unavailable, it is difficult to analyze the in-vitro assay results and determine the parameters that predict disease response.
point of contact: 