<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/NCT01711528</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-01737</org_study_id>
    <secondary_id>NCI-2012-01737</secondary_id>
    <secondary_id>MC1113</secondary_id>
    <secondary_id>NCI 9157</secondary_id>
    <secondary_id>CDR0000741989</secondary_id>
    <secondary_id>MC1113</secondary_id>
    <secondary_id>9157</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <secondary_id>R01CA167511</secondary_id>
    <secondary_id>U01CA069912</secondary_id>
    <secondary_id>UM1CA186686</secondary_id>
    <secondary_id>UM1CA186716</secondary_id>
    <nct_id>NCT01711528</nct_id>
    <nct_alias>NCT02668731</nct_alias>
  </id_info>
  <brief_title>Dinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma</brief_title>
  <official_title>Phase 1 Clinical Trial of a Novel CDK Inhibitor Dinaciclib (SCH 727965) in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of dinaciclib and bortezomib when&#xD;
      given together with dexamethasone in treating patients with multiple myeloma that has&#xD;
      returned after a period of improvement. Dinaciclib and bortezomib may stop the growth of&#xD;
      cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in&#xD;
      chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving dinaciclib and bortezomib together with dexamethasone may kill more cancer&#xD;
      cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximally tolerated doses of dinaciclib and bortezomib, when used in&#xD;
      combination, in two different schedules, for treatment of relapsed multiple myeloma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the toxicities associated with dinaciclib and bortezomib, when used in&#xD;
      combination, for treatment of relapsed multiple myeloma.&#xD;
&#xD;
      II. To determine the overall response rate associated with dinaciclib and bortezomib, when&#xD;
      used in combination, for treatment of relapsed multiple myeloma.&#xD;
&#xD;
      III. To explore the differences in toxicity associated with two different schedules of&#xD;
      dinaciclib and bortezomib used in combination.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To examine if expression levels of target cyclin dependent kinase (CDK): CDK 2,5,7 and 9&#xD;
      levels in cluster of differentiation (CD)138-purified tumor cells, will be correlated with&#xD;
      response (clinical and molecular) to determine if high or low level target CDK expression, if&#xD;
      present, influences dinaciclib efficacy.&#xD;
&#xD;
      II. To examine if immunoglobulin (Ig)H translocation status, P53 status and presence of v-myc&#xD;
      myelocytomatosis viral oncogene homolog (avian) (Myc) amplification or rearrangement,&#xD;
      determined on patient bone marrow before treatment, using a pre validated fluorescence in&#xD;
      situ hybridization (FISH) panel to identify common myeloma translocations, will be correlated&#xD;
      with molecular and/or clinical markers of drug activity, and to assess if specific genetic&#xD;
      subgroups of myeloma tumors are responsive or resistant.&#xD;
&#xD;
      III. To determine the gene expression profiles of myeloma cells before and after treatment to&#xD;
      understand the role of tumor gene dysregulation and/or dinaciclib induced effects on&#xD;
      transcription.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of dinaciclib and bortezomib. Patients are assigned&#xD;
      to 1 of 2 treatment schedules.&#xD;
&#xD;
      SCHEDULE I: Patients receive dinaciclib intravenously (IV) over 2 hours and bortezomib&#xD;
      subcutaneously (SC) or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and&#xD;
      dexamethasone orally (PO) once daily (QD) on days 1, 2, 8, 9, 15, and 16. Courses repeat&#xD;
      every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      SCHEDULE II: Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1&#xD;
      and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2012</start_date>
  <completion_date type="Actual">November 22, 2016</completion_date>
  <primary_completion_date type="Actual">November 22, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MTD of dinaciclib and bortezomib when given together with dexamethasone, based on the incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>MTD is defined as the dose level below the lowest dose that induces DLT in at least one-third of patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events, graded according to NCT CTCAE version 4.0</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. Toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>Summarized descriptively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure</measure>
    <time_frame>From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patients, assessed up to 3 months</time_frame>
    <description>Summarized descriptively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>Summarized descriptively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Schedule I (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive dinaciclib IV over 2 hours and bortezomib SC or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and dexamethasone PO QD on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Schedule II (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1 and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Schedule I (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <arm_group_label>Schedule II (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <other_name>[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid</other_name>
    <other_name>LDP 341</other_name>
    <other_name>MLN341</other_name>
    <other_name>PS-341</other_name>
    <other_name>PS341</other_name>
    <other_name>Velcade</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Schedule I (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <arm_group_label>Schedule II (dinaciclib, bortezomib, dexamethasone)</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>Drug</intervention_type>
    <intervention_name>Dinaciclib</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Schedule I (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <arm_group_label>Schedule II (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <other_name>CDK Inhibitor SCH 727965</other_name>
    <other_name>MK-7965</other_name>
    <other_name>SCH 727965</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Schedule I (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
    <arm_group_label>Schedule II (dinaciclib, bortezomib, dexamethasone)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Serum creatinine =&lt; 2.5 mg/dL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1000/uL&#xD;
&#xD;
          -  Untransfused platelet count &gt;= 75000/uL&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 times institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Patients with relapsed multiple myeloma who have already received one or more standard&#xD;
             treatment regimens&#xD;
&#xD;
          -  Measurable disease of multiple myeloma as defined by at least ONE of the following:&#xD;
&#xD;
               -  Serum monoclonal protein &gt;= 1 g/dL&#xD;
&#xD;
               -  &gt;= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis&#xD;
&#xD;
               -  Serum immunoglobulin free light chain &gt;= 10 mg/dL and abnormal serum&#xD;
                  immunoglobulin kappa to lambda free light chain ratio&#xD;
&#xD;
               -  Monoclonal bone marrow plasmacytosis &gt;= 30% (evaluable disease)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2&#xD;
&#xD;
          -  Adequate residual organ function per treating physician discretion; Note: there is no&#xD;
             limit with regard to the number of prior therapies&#xD;
&#xD;
          -  Provide informed written consent&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Willing to provide samples for correlative research purposes&#xD;
&#xD;
          -  Willing to return to consenting institution for follow-up during the study&#xD;
&#xD;
          -  Recovered (i.e., =&lt; grade 1 toxicity) from the reversible effects of prior&#xD;
             antineoplastic therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following recent therapies:&#xD;
&#xD;
               -  Alkylators (e.g. melphalan, cyclophosphamide) =&lt; 14 days prior to registration&#xD;
&#xD;
               -  Anthracyclines =&lt; 14 days prior to registration&#xD;
&#xD;
               -  High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide),&#xD;
                  or proteosome inhibitors (bortezomib) =&lt; 7 days prior to registration&#xD;
&#xD;
          -  Concomitant high dose corticosteroids (concurrent use of corticosteroids); EXCEPTION:&#xD;
             patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if&#xD;
             they are being given for disorders other than amyloid, i.e., adrenal insufficiency,&#xD;
             rheumatoid arthritis, etc.&#xD;
&#xD;
          -  Other active malignancy =&lt; 2 years prior to registration; EXCEPTIONS: non-melanotic&#xD;
             skin cancer or carcinoma in-situ of the cervix; NOTE: if there is a history of prior&#xD;
             malignancy, they must not be receiving other specific treatment for their cancer&#xD;
&#xD;
          -  Any of the following:&#xD;
&#xD;
               -  Pregnant women or women of reproductive ability who are unwilling to use 2&#xD;
                  effective methods of contraception from the time of signing the informed consent&#xD;
                  form through 30 days after the last dose of study drug&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men who are unwilling to use a condom (even if they have undergone a prior&#xD;
                  vasectomy) while having intercourse with any woman, while taking the drug and for&#xD;
                  30 days after stopping treatment&#xD;
&#xD;
          -  Other co-morbidity which would interfere with patient's ability to participate in&#xD;
             trial, e.g. uncontrolled infection, uncompensated heart or lung disease&#xD;
&#xD;
          -  Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered&#xD;
             investigational; NOTE: bisphosphonates are considered to be supportive care rather&#xD;
             than therapy, and are thus allowed while on protocol treatment&#xD;
&#xD;
          -  Peripheral neuropathy &gt;= grade 2 on clinical examination during the screening period&#xD;
&#xD;
          -  Major surgery =&lt; 14 days prior to registration&#xD;
&#xD;
          -  Currently taking strong or moderate inhibitors/inducers of cytochrome P450, family 3,&#xD;
             subfamily A, polypeptide 4 (CYP3A4); Note: dinaciclib is a CYP3A4 substrate; patients&#xD;
             should not take grapefruit/grapefruit juice or St. John's wort; use of strong or&#xD;
             moderate CYP3A4 inhibitors is prohibited from &lt; 7 days prior to registration; use of&#xD;
             CYP3A4 inducers is prohibited from =&lt; 7 days prior to registration&#xD;
&#xD;
          -  Any of the following conditions:&#xD;
&#xD;
               -  Myocardial infarction =&lt; 6 months prior to registration or has New York Heart&#xD;
                  Association (NYHA) class III or IV heart failure&#xD;
&#xD;
               -  Uncontrolled angina&#xD;
&#xD;
               -  Severe uncontrolled ventricular arrhythmias&#xD;
&#xD;
               -  Electrocardiographic evidence of acute ischemia&#xD;
&#xD;
               -  Active conduction system abnormalities; NOTE: prior to study entry, any&#xD;
                  electrocardiogram (ECG) abnormality at screening must be documented by the&#xD;
                  investigator as not medically relevant&#xD;
&#xD;
          -  Known hypersensitivity to bortezomib, boron, or mannitol&#xD;
&#xD;
          -  Serious medical or psychiatric illness likely to interfere with participation in this&#xD;
             clinical study per the judgment of the treating physician&#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>Shaji Kumar</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Hospital and Clinics</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aspirus UW Cancer Center</name>
      <address>
        <city>Wisconsin Rapids</city>
        <state>Wisconsin</state>
        <zip>54494</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>May 10, 2018</last_update_submitted>
  <last_update_submitted_qc>May 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Ichthammol</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01711528
org study id: NCI-2012-01737
secondary id: NCI-2012-01737
secondary id: MC1113
secondary id: NCI 9157
secondary id: CDR0000741989
secondary id: MC1113
secondary id: 9157
secondary id: P30CA015083
secondary id: R01CA167511
secondary id: U01CA069912
secondary id: UM1CA186686
secondary id: UM1CA186716
nct id: NCT01711528
nct alias: NCT02668731
lead sponsor: 
This phase I trial studies the side effects and best dose of dinaciclib and bortezomib when
      given together with dexamethasone in treating patients with multiple myeloma that has
      returned after a period of improvement. Dinaciclib and bortezomib may stop the growth of
      cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy, such as 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. Giving dinaciclib and bortezomib together with dexamethasone may kill more cancer
      cells.
PRIMARY OBJECTIVES:

      I. To determine the maximally tolerated doses of dinaciclib and bortezomib, when used in
      combination, in two different schedules, for treatment of relapsed multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To determine the toxicities associated with dinaciclib and bortezomib, when used in
      combination, for treatment of relapsed multiple myeloma.

      II. To determine the overall response rate associated with dinaciclib and bortezomib, when
      used in combination, for treatment of relapsed multiple myeloma.

      III. To explore the differences in toxicity associated with two different schedules of
      dinaciclib and bortezomib used in combination.

      TERTIARY OBJECTIVES:

      I. To examine if expression levels of target cyclin dependent kinase (CDK): CDK 2,5,7 and 9
      levels in cluster of differentiation (CD)138-purified tumor cells, will be correlated with
      response (clinical and molecular) to determine if high or low level target CDK expression, if
      present, influences dinaciclib efficacy.

      II. To examine if immunoglobulin (Ig)H translocation status, P53 status and presence of v-myc
      myelocytomatosis viral oncogene homolog (avian) (Myc) amplification or rearrangement,
      determined on patient bone marrow before treatment, using a pre validated fluorescence in
      situ hybridization (FISH) panel to identify common myeloma translocations, will be correlated
      with molecular and/or clinical markers of drug activity, and to assess if specific genetic
      subgroups of myeloma tumors are responsive or resistant.

      III. To determine the gene expression profiles of myeloma cells before and after treatment to
      understand the role of tumor gene dysregulation and/or dinaciclib induced effects on
      transcription.

      OUTLINE: This is a dose-escalation study of dinaciclib and bortezomib. Patients are assigned
      to 1 of 2 treatment schedules.

      SCHEDULE I: Patients receive dinaciclib intravenously (IV) over 2 hours and bortezomib
      subcutaneously (SC) or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and
      dexamethasone orally (PO) once daily (QD) on days 1, 2, 8, 9, 15, and 16. Courses repeat
      every 28 days in the absence of disease progression or unacceptable toxicity.

      SCHEDULE II: Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1
      and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and 3 months.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTD of dinaciclib and bortezomib when given together with dexamethasone, based on the incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: Up to 28 days
description: MTD is defined as the dose level below the lowest dose that induces DLT in at least one-third of patients.
measure: Incidence of adverse events, graded according to NCT CTCAE version 4.0
time frame: Up to 3 months
description: The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. Toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
measure: Overall response rate
time frame: Up to 3 months
description: Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
measure: Time to progression
time frame: Up to 3 months
description: Summarized descriptively.
measure: Time to treatment failure
time frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patients, assessed up to 3 months
description: Summarized descriptively.
measure: Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)
time frame: Up to 3 months
description: Summarized descriptively.
arm group label: Schedule I (dinaciclib, bortezomib, dexamethasone)
arm group type: Experimental
description: Patients receive dinaciclib IV over 2 hours and bortezomib SC or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and dexamethasone PO QD on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
arm group label: Schedule II (dinaciclib, bortezomib, dexamethasone)
arm group type: Experimental
description: Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1 and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Bortezomib
description: Given SC
arm group label: Schedule I (dinaciclib, bortezomib, dexamethasone)
arm group label: Schedule II (dinaciclib, bortezomib, dexamethasone)
other name: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
other name: LDP 341
other name: MLN341
other name: PS-341
other name: PS341
other name: Velcade
intervention type: Drug
intervention name: Dexamethasone
description: Given PO
arm group label: Schedule I (dinaciclib, bortezomib, dexamethasone)
arm group label: Schedule II (dinaciclib, bortezomib, dexamethasone)
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: Drug
intervention name: Dinaciclib
description: Given IV
arm group label: Schedule I (dinaciclib, bortezomib, dexamethasone)
arm group label: Schedule II (dinaciclib, bortezomib, dexamethasone)
other name: CDK Inhibitor SCH 727965
other name: MK-7965
other name: SCH 727965
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Schedule I (dinaciclib, bortezomib, dexamethasone)
arm group label: Schedule II (dinaciclib, bortezomib, dexamethasone)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shaji Kumar
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Bortezomib
mesh term: Ichthammol
mesh term: BB 1101