<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/NCT02206425</url>
  </required_header>
  <id_info>
    <org_study_id>X16041</org_study_id>
    <secondary_id>IISR-2013-M100118</secondary_id>
    <nct_id>NCT02206425</nct_id>
  </id_info>
  <brief_title>Ixazomib as a Replacement for Carfilzomib and Bortezomib for Multiple Myeloma Patients</brief_title>
  <official_title>A Phase 1/2 Study of Ixazomib as a Replacement for Bortezomib or Carfilzomib for Multiple Myeloma (MM) Patients Recently Relapsed or Refractory to Their Last Combination Regimen Containing Either Bortezomib or Carfilzomib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncotherapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Oncotherapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this clinical research study is to evaluate the safety and effectiveness (good&#xD;
      and bad effects) of ixazomib given as part of a combination therapy to treat subjects with&#xD;
      relapsed (subjects whose disease came back) or refractory (subjects whose disease did not&#xD;
      respond to past treatment) multiple myeloma. More specifically, the study is focused on&#xD;
      subjects who were previously treated with bortezomib (Velcade®) or carfilzomib (Kyprolis®)&#xD;
      and showed worsening of their myeloma while receiving either one of these drugs in&#xD;
      combination therapy. This study is a Phase I/II. Ixazomib is an investigational drug, which&#xD;
      means that ixazomib is currently being tested and is not yet approved by the United States&#xD;
      Food and Drug Administration (FDA) for subjects with relapsed or refractory multiple myeloma.&#xD;
      Ixazomib is a new study drug that belongs to the same class as bortezomib and carfilzomib;&#xD;
      however, unlike bortezomib and carfilzomib, ixazomib is taken by mouth. Current studies&#xD;
      investigating ixazomib are demonstrating that it is as safe as bortezomib and effective for&#xD;
      the treatment of multiple myeloma both on its own and in combination with other multiple&#xD;
      myeloma medications, such as lenalidomide and dexamethasone, or prednisone and melphalan.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1/2, intra-patient, multicenter, open-label and non-randomized study to&#xD;
      evaluate the efficacy and safety of ixazomib as a replacement for bortezomib or carfilzomib&#xD;
      among multiple myeloma (MM) patients who have failed proteasome inhibitor (PI)-containing&#xD;
      combination regimens. Patients will receive ixazomib once a week in place of bortezomib or&#xD;
      carfilzomib in combination with an alkylating agent (melphalan or cyclophosphamide),&#xD;
      anthracycline (pegylated doxorubicin [PLD]), immunomodulatory agent (lenalidomide,&#xD;
      pomalidomide), ascorbic acid and/or a glucocorticosteroid (dexamethasone, prednisone or&#xD;
      methylprednisolone) administered using the same dose(s) and schedule(s) as the last&#xD;
      PI-containing regimen that the patients had received and failed. The total number of&#xD;
      different prior bortezomib- or carfilzomib-containing regimens that will be evaluated is 10,&#xD;
      reflecting those commonly used in the community as follows:&#xD;
&#xD;
        -  bortezomib + melphalan + prednisone&#xD;
&#xD;
        -  bortezomib + cyclophosphamide + ascorbic acid&#xD;
&#xD;
        -  bortezomib + cyclophosphamide + dexamethasone&#xD;
&#xD;
        -  bortezomib + PLD + dexamethasone&#xD;
&#xD;
        -  bortezomib + dexamethasone&#xD;
&#xD;
        -  carfilzomib + dexamethasone&#xD;
&#xD;
        -  bortezomib + lenalidomide + dexamethasone&#xD;
&#xD;
        -  bortezomib + pomalidomide + dexamethasone&#xD;
&#xD;
        -  carfilzomib + lenalidomide + dexamethasone&#xD;
&#xD;
        -  carfilzomib + pomalidomide + dexamethasone&#xD;
&#xD;
      This study will enroll 60 patients who are refractory to a bortezomib- or&#xD;
      carfilzomib-containing combination regimen, as demonstrated by progressive disease (PD) while&#xD;
      being treated, or who have relapsed within 8 weeks from the last dose of bortezomib or&#xD;
      carfilzomib in their last PI-containing combination regimen.&#xD;
&#xD;
      Ixazomib will replace bortezomib or carfilzomib using the same PI-containing regimen the&#xD;
      patients failed.The study will consist of: 1) a screening period; 2) up to eight 28-day&#xD;
      treatment cycles; 3) a maintenance period; 4) a final assessment to occur 28 days after the&#xD;
      end of the last treatment cycle; and 5) a follow-up period.&#xD;
&#xD;
      Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle to patients&#xD;
      enrolled in seven regimens (bortezomib + melphalan + prednisone, bortezomib + dexamethasone,&#xD;
      carfilzomib + dexamethasone, bortezomib + lenalidomide + dexamethasone, bortezomib +&#xD;
      pomalidomide + dexamethasone, carfilzomib + lenalidomide + dexamethasone, carfilzomib +&#xD;
      pomalidomide + dexamethasone). Subjects on those regimens receiving 4 mg of ixazomib from the&#xD;
      beginning of the trial will continue to do so for the length of the study, unless they suffer&#xD;
      from adverse events requiring dose reductions. For the other three regimens, bortezomib +&#xD;
      cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, and&#xD;
      bortezomib + PLD + dexamethasone, the MTD for ixazomib is unknown and intra-patient dose&#xD;
      escalation will be performed to determine the specific MTD for each of them. For these three&#xD;
      regimens, ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting&#xD;
      dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle&#xD;
      2. All other agents will be administered at the same schedule and dose intensity as those of&#xD;
      the last PI-containing treatment the patient failed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Anticipated">September 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Maximum tolerated dose (MTD) for selected regimens</measure>
    <time_frame>Cycles 1-2 for selected regimens (up to 2 months)</time_frame>
    <description>MTD determined via the number of dose-limiting toxicities (DLTs) per cohort for the following ixazomib- containing combinations:&#xD;
bortezomib+ cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, bortezomib + PLD + dexamethasone</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 48 months</time_frame>
    <description>Occurrence of adverse events throughout the study, graded via CTCAE v 4.03 criteria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>up to 48 months</time_frame>
    <description>Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using IMWG criteria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical benefit rate (CBR)</measure>
    <time_frame>up to 48 months</time_frame>
    <description>CBR=ORR + minor response (MR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>at least over 48 months</time_frame>
    <description>Time from initiation of therapy to progressive disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>at least over 48 months</time_frame>
    <description>Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>up to 48 months</time_frame>
    <description>Time from the initiation of therapy to the first evidence of a confirmed response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>at least over 48 months</time_frame>
    <description>Time from the first response (&gt; PR) to progressive disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>at least over 48 months</time_frame>
    <description>Time from initiation of therapy to death from any cause or last follow-up visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral Neuropathy (PN)</measure>
    <time_frame>up to 48 months</time_frame>
    <description>Incidence and severity among patients receiving ixazomib compared to their baseline PN when they entered the trial, defined by CTCAE v4.0.3 and FACT-GOG/NTX questionnaire score.</description>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>bortezomib + melphalan + prednisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bortezomib + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>carfilzomib + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bortezomib + lenalidomide + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>carfilzomib + lenalidomide + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bortezomib + cyclophosphamide + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bortezomib + cyclophosphamide + ascorbic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Due to a potential drug-drug interaction between ixazomib and ascorbic acid, patients will receive ixazomib in the clinic in the morning and will be instructed to take ascorbic acid in the evening, followed by cyclophosphamide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bortezomib + PLD + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bortezomib + pomalidomide + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>carfilzomib + pomalidomide + dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Melphalan will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + melphalan + prednisone</arm_group_label>
    <other_name>Phenylalanine mustard</other_name>
    <other_name>Alkeran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + melphalan + prednisone</arm_group_label>
    <other_name>Cortan</other_name>
    <other_name>Deltasone</other_name>
    <other_name>Orasone</other_name>
    <other_name>Prednisone Intensol</other_name>
    <other_name>Sterapred</other_name>
    <other_name>Sterapred DS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + cyclophosphamide + ascorbic acid</arm_group_label>
    <arm_group_label>bortezomib + cyclophosphamide + dexamethasone</arm_group_label>
    <other_name>Cytoxan</other_name>
    <other_name>CPM</other_name>
    <other_name>CTX</other_name>
    <other_name>CYT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + PLD + dexamethasone</arm_group_label>
    <arm_group_label>bortezomib + cyclophosphamide + dexamethasone</arm_group_label>
    <arm_group_label>bortezomib + dexamethasone</arm_group_label>
    <arm_group_label>bortezomib + lenalidomide + dexamethasone</arm_group_label>
    <arm_group_label>bortezomib + pomalidomide + dexamethasone</arm_group_label>
    <arm_group_label>carfilzomib + dexamethasone</arm_group_label>
    <arm_group_label>carfilzomib + lenalidomide + dexamethasone</arm_group_label>
    <arm_group_label>carfilzomib + pomalidomide + dexamethasone</arm_group_label>
    <other_name>Decadron</other_name>
    <other_name>Dexamethasone Intensol</other_name>
    <other_name>Dexpak Taperpak</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Ascorbic acid</intervention_name>
    <description>Vitamin C will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + cyclophosphamide + ascorbic acid</arm_group_label>
    <other_name>Vitamin C</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PLD</intervention_name>
    <description>Pegylated liposomal doxorubicin will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + PLD + dexamethasone</arm_group_label>
    <other_name>ATI-0918</other_name>
    <other_name>doxorubicin hydrochloride liposome</other_name>
    <other_name>doxorubicin hydrochloride liposome injection</other_name>
    <other_name>liposomal adriamycin</other_name>
    <other_name>liposomal doxorubicin</other_name>
    <other_name>liposomal doxorubicin hydrochloride</other_name>
    <other_name>liposome-encapsulated doxorubicin</other_name>
    <other_name>pegylated doxorubicin HCl liposome</other_name>
    <other_name>Pegylated Liposomal Doxorubicin</other_name>
    <other_name>S-Liposomal Doxorubicin</other_name>
    <other_name>Stealth Liposomal Doxorubicin</other_name>
    <other_name>DOXIL</other_name>
    <other_name>Dox-SL</other_name>
    <other_name>Evacet</other_name>
    <other_name>LipoDox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Lenalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + lenalidomide + dexamethasone</arm_group_label>
    <arm_group_label>carfilzomib + lenalidomide + dexamethasone</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>Pomalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).</description>
    <arm_group_label>bortezomib + pomalidomide + dexamethasone</arm_group_label>
    <arm_group_label>carfilzomib + pomalidomide + dexamethasone</arm_group_label>
    <other_name>Pomalyst</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients 18 years or older&#xD;
&#xD;
          2. Patients must have a diagnosis of MM, based on standard criteria as follows:&#xD;
&#xD;
               -  Major criteria:&#xD;
&#xD;
                    1. plasmacytomas on tissue biopsy&#xD;
&#xD;
                    2. bone marrow plasmacytosis (greater than 30% plasma cells)&#xD;
&#xD;
                    3. monoclonal immunoglobulin spike on serum electrophoresis IgG greater than&#xD;
                       3.5 g/dL or IgA greater than 2.0 g/dL; kappa or lambda light chain excretion&#xD;
                       greater than 1 g/day on 24 hour urine protein electrophoresis&#xD;
&#xD;
               -  Minor criteria:&#xD;
&#xD;
                    1. bone marrow plasmacytosis (10% to 30% plasma cells)&#xD;
&#xD;
                    2. monoclonal immunoglobulin present but of lesser magnitude than given under&#xD;
                       major criteria&#xD;
&#xD;
                    3. lytic bone lesions&#xD;
&#xD;
                    4. normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600&#xD;
                       mg/dL&#xD;
&#xD;
             Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:&#xD;
&#xD;
               -  any 2 of the major criteria&#xD;
&#xD;
               -  major criterion 1 plus minor criterion 2, 3, or 4&#xD;
&#xD;
               -  major criterion 3 plus minor criterion 1 or 3&#xD;
&#xD;
               -  minor criteria 1, 2, and 3, or 1, 2, and 4&#xD;
&#xD;
          3. Currently has progressive MM that has previously progressed or is currently&#xD;
             progressing while receiving or within 8 weeks of receiving bortezomib or carfilzomib&#xD;
             as part of a combination treatment. MM patients that demonstrate refractory disease,&#xD;
             as defined below, are both eligible for enrollment provided they fulfill the other&#xD;
             eligibility criteria:&#xD;
&#xD;
             • Patients are refractory to a bortezomib or carfilzomib combination regimen, when&#xD;
             they progress while currently receiving a bortezomib or carfilzomib combination&#xD;
             treatment, or within 8 weeks of its last dose. Patients are considered relapsed, when&#xD;
             they progress between 8 and 12-weeks from their last dose of bortezomib or carfilzomib&#xD;
             as part of a bortezomib or carfilzomib combination therapy. Prior treatment with four&#xD;
             days or less of a total of 400 mg of prednisone (or an equivalent potency of another&#xD;
             steroid) for MM will not be considered a regimen.&#xD;
&#xD;
          4. Patients that were on bortezomib-containing regimens must have been administered at&#xD;
             least 4 doses of a minimum of 1.0 mg/m2 in no more than 28-days cycles. Subjects must&#xD;
             have received at least one cycle meeting this definition and have shown PD to be&#xD;
             considered eligible&#xD;
&#xD;
          5. Patients that were on carfilzomib-containing regimens must have received at least 6&#xD;
             doses of at least 27 mg/m2 in no more than 28 days per cycle. Subjects must have&#xD;
             received at least one cycle meeting this definition and have shown PD to be considered&#xD;
             eligible&#xD;
&#xD;
          6. Progressed from one of the specific bortezomib- or carfilzomib-containing regimens as&#xD;
             listed on page 51. Although bortezomib- and carfilzomib-containing combination&#xD;
             regimens that are otherwise identical except for the PI result in the same ixazomib&#xD;
             regimen, they will be enrolled separately so that safety/efficacy can be separately&#xD;
             determined, thereby allowing comparisons based on the prior PI that subjects were&#xD;
             exposed to as part of the regimen that they failed (carfilzomib vs. bortezomib)&#xD;
&#xD;
          7. Patient may have received a carfilzomib- or bortezomib-containing regimen at any time&#xD;
             and may have received other non-proteasome inhibitor-containing intervening treatments&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Patient has been diagnosed with:&#xD;
&#xD;
               1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,&#xD;
                  monoclonal protein (M protein) and skin changes (POEMS) syndrome.3&#xD;
&#xD;
               2. Primary amyloidosis&#xD;
&#xD;
               3. Plasma cell leukemia&#xD;
&#xD;
               4. Severe hypercalcemia, i.e., serum calcium = 12 mg/dL (3.0 mmol/L) corrected for&#xD;
                  albumin&#xD;
&#xD;
          2. Diagnosed or treated for another malignancy within 3 years before study enrollment or&#xD;
             previously diagnosed with another malignancy and have any evidence of residual&#xD;
             disease. Patients with non-melanomatous skin cancer or carcinoma in situ of any type&#xD;
             are not excluded if they have undergone complete resection.&#xD;
&#xD;
          3. Impaired cardiac function or clinically significant cardiac diseases, including&#xD;
             myocardial infarction within 6 months prior to enrollment, New York Heart Association&#xD;
             (NYHA) Class II or greater heart failure, uncontrolled angina, clinically significant&#xD;
             pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or&#xD;
             multigated acquisition scan (MUGA) evidence of left ventricular ejection fraction&#xD;
             (LVEF) below institutional normal within 28 days prior to enrollment,&#xD;
             electrocardiographic evidence of acute ischemia or active conduction system&#xD;
             abnormalities. Prior to study entry, any ECG abnormality at Screening has to be&#xD;
             documented by the investigator as not medically relevant&#xD;
&#xD;
          4. Patient has peripheral neuropathy grade 3 or higher or Grade 2 with pain on clinical&#xD;
             examination during the screening period&#xD;
&#xD;
          5. Patient has received the following prior therapy:&#xD;
&#xD;
               1. Chemotherapy within 21 days of enrollment (6 weeks for nitrosoureas)&#xD;
&#xD;
               2. Corticosteroids (&gt;10 mg/day prednisone or equivalent) within 21 days of&#xD;
                  enrollment&#xD;
&#xD;
               3. Immunotherapy or antibody therapy as well as thalidomide, pomalidomide,&#xD;
                  lenalidomide, arsenic trioxide, carfilzomib, or bortezomib within 21 days before&#xD;
                  enrollment&#xD;
&#xD;
          6. Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
             various formulations of any agent&#xD;
&#xD;
          7. Known GI disease or GI procedure that could interfere with the oral absorption or&#xD;
             tolerance of ixazomib including difficulty swallowing&#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>James R Berenson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>James R. Berenson MD, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Comprehensive Blood and Cancer Center</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Muir Health Clinical Research Center</name>
      <address>
        <city>Concord</city>
        <state>California</state>
        <zip>94520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Cancer Associates for Research &amp; Excellence (cCARE)</name>
      <address>
        <city>Encinitas</city>
        <state>California</state>
        <zip>92024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert A. Moss, MD, FACP, Inc</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>cCARE Fresno</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Center at Desert Regional Medical Center</name>
      <address>
        <city>Palm Springs</city>
        <state>California</state>
        <zip>92262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James Berenson, MD, Inc</name>
      <address>
        <city>West Hollywood</city>
        <state>California</state>
        <zip>90069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Specialists of North Florida</name>
      <address>
        <city>Fleming Island</city>
        <state>Florida</state>
        <zip>32003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lewis Hall Singletary Oncology Center</name>
      <address>
        <city>Thomasville</city>
        <state>Georgia</state>
        <zip>31792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Specialists, SC</name>
      <address>
        <city>Niles</city>
        <state>Illinois</state>
        <zip>60714</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hattiesburg Clinic Hematology/Oncology</name>
      <address>
        <city>Hattiesburg</city>
        <state>Mississippi</state>
        <zip>39401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vista Oncology</name>
      <address>
        <city>Olympia</city>
        <state>Washington</state>
        <zip>98502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>August 13, 2020</last_update_submitted>
  <last_update_submitted_qc>August 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>multiple myeloma</keyword>
  <keyword>Relapsed/refractory</keyword>
  <keyword>Ixazomib</keyword>
  <keyword>Proteasome inhibitor</keyword>
  <keyword>Oral</keyword>
  <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>Ascorbic Acid</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Pomalidomide</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/NCT02206425
org study id: X16041
secondary id: IISR-2013-M100118
nct id: NCT02206425
lead sponsor: 
collaborator: 
has dmc: Yes
The goal of this clinical research study is to evaluate the safety and effectiveness (good
      and bad effects) of ixazomib given as part of a combination therapy to treat subjects with
      relapsed (subjects whose disease came back) or refractory (subjects whose disease did not
      respond to past treatment) multiple myeloma. More specifically, the study is focused on
      subjects who were previously treated with bortezomib (Velcade®) or carfilzomib (Kyprolis®)
      and showed worsening of their myeloma while receiving either one of these drugs in
      combination therapy. This study is a Phase I/II. Ixazomib is an investigational drug, which
      means that ixazomib is currently being tested and is not yet approved by the United States
      Food and Drug Administration (FDA) for subjects with relapsed or refractory multiple myeloma.
      Ixazomib is a new study drug that belongs to the same class as bortezomib and carfilzomib;
      however, unlike bortezomib and carfilzomib, ixazomib is taken by mouth. Current studies
      investigating ixazomib are demonstrating that it is as safe as bortezomib and effective for
      the treatment of multiple myeloma both on its own and in combination with other multiple
      myeloma medications, such as lenalidomide and dexamethasone, or prednisone and melphalan.
This is a phase 1/2, intra-patient, multicenter, open-label and non-randomized study to
      evaluate the efficacy and safety of ixazomib as a replacement for bortezomib or carfilzomib
      among multiple myeloma (MM) patients who have failed proteasome inhibitor (PI)-containing
      combination regimens. Patients will receive ixazomib once a week in place of bortezomib or
      carfilzomib in combination with an alkylating agent (melphalan or cyclophosphamide),
      anthracycline (pegylated doxorubicin [PLD]), immunomodulatory agent (lenalidomide,
      pomalidomide), ascorbic acid and/or a glucocorticosteroid (dexamethasone, prednisone or
      methylprednisolone) administered using the same dose(s) and schedule(s) as the last
      PI-containing regimen that the patients had received and failed. The total number of
      different prior bortezomib- or carfilzomib-containing regimens that will be evaluated is 10,
      reflecting those commonly used in the community as follows:

        -  bortezomib + melphalan + prednisone

        -  bortezomib + cyclophosphamide + ascorbic acid

        -  bortezomib + cyclophosphamide + dexamethasone

        -  bortezomib + PLD + dexamethasone

        -  bortezomib + dexamethasone

        -  carfilzomib + dexamethasone

        -  bortezomib + lenalidomide + dexamethasone

        -  bortezomib + pomalidomide + dexamethasone

        -  carfilzomib + lenalidomide + dexamethasone

        -  carfilzomib + pomalidomide + dexamethasone

      This study will enroll 60 patients who are refractory to a bortezomib- or
      carfilzomib-containing combination regimen, as demonstrated by progressive disease (PD) while
      being treated, or who have relapsed within 8 weeks from the last dose of bortezomib or
      carfilzomib in their last PI-containing combination regimen.

      Ixazomib will replace bortezomib or carfilzomib using the same PI-containing regimen the
      patients failed.The study will consist of: 1) a screening period; 2) up to eight 28-day
      treatment cycles; 3) a maintenance period; 4) a final assessment to occur 28 days after the
      end of the last treatment cycle; and 5) a follow-up period.

      Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle to patients
      enrolled in seven regimens (bortezomib + melphalan + prednisone, bortezomib + dexamethasone,
      carfilzomib + dexamethasone, bortezomib + lenalidomide + dexamethasone, bortezomib +
      pomalidomide + dexamethasone, carfilzomib + lenalidomide + dexamethasone, carfilzomib +
      pomalidomide + dexamethasone). Subjects on those regimens receiving 4 mg of ixazomib from the
      beginning of the trial will continue to do so for the length of the study, unless they suffer
      from adverse events requiring dose reductions. For the other three regimens, bortezomib +
      cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, and
      bortezomib + PLD + dexamethasone, the MTD for ixazomib is unknown and intra-patient dose
      escalation will be performed to determine the specific MTD for each of them. For these three
      regimens, ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting
      dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle
      2. All other agents will be administered at the same schedule and dose intensity as those of
      the last PI-containing treatment the patient failed.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) for selected regimens
time frame: Cycles 1-2 for selected regimens (up to 2 months)
description: MTD determined via the number of dose-limiting toxicities (DLTs) per cohort for the following ixazomib- containing combinations:
bortezomib+ cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, bortezomib + PLD + dexamethasone
measure: Number of subjects with adverse events
time frame: up to 48 months
description: Occurrence of adverse events throughout the study, graded via CTCAE v 4.03 criteria
measure: Overall response rate (ORR)
time frame: up to 48 months
description: Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using IMWG criteria
measure: Clinical benefit rate (CBR)
time frame: up to 48 months
description: CBR=ORR + minor response (MR)
measure: Time to Progression
time frame: at least over 48 months
description: Time from initiation of therapy to progressive disease
measure: Progression-free survival (PFS)
time frame: at least over 48 months
description: Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
measure: Time to response (TTR)
time frame: up to 48 months
description: Time from the initiation of therapy to the first evidence of a confirmed response
measure: Duration of response (DOR)
time frame: at least over 48 months
description: Time from the first response (> PR) to progressive disease
measure: Overall survival (OS)
time frame: at least over 48 months
description: Time from initiation of therapy to death from any cause or last follow-up visit
measure: Peripheral Neuropathy (PN)
time frame: up to 48 months
description: Incidence and severity among patients receiving ixazomib compared to their baseline PN when they entered the trial, defined by CTCAE v4.0.3 and FACT-GOG/NTX questionnaire score.
arm group label: bortezomib + melphalan + prednisone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: bortezomib + dexamethasone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: carfilzomib + dexamethasone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: bortezomib + lenalidomide + dexamethasone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: carfilzomib + lenalidomide + dexamethasone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: bortezomib + cyclophosphamide + dexamethasone
arm group type: Experimental
description: MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: bortezomib + cyclophosphamide + ascorbic acid
arm group type: Experimental
description: MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Due to a potential drug-drug interaction between ixazomib and ascorbic acid, patients will receive ixazomib in the clinic in the morning and will be instructed to take ascorbic acid in the evening, followed by cyclophosphamide.
arm group label: bortezomib + PLD + dexamethasone
arm group type: Experimental
description: MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: bortezomib + pomalidomide + dexamethasone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
arm group label: carfilzomib + pomalidomide + dexamethasone
arm group type: Experimental
description: Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib.
intervention type: Drug
intervention name: Melphalan
description: Melphalan will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + melphalan + prednisone
other name: Phenylalanine mustard
other name: Alkeran
intervention type: Drug
intervention name: Prednisone
description: Prednisone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + melphalan + prednisone
other name: Cortan
other name: Deltasone
other name: Orasone
other name: Prednisone Intensol
other name: Sterapred
other name: Sterapred DS
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + cyclophosphamide + ascorbic acid
arm group label: bortezomib + cyclophosphamide + dexamethasone
other name: Cytoxan
other name: CPM
other name: CTX
other name: CYT
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + PLD + dexamethasone
arm group label: bortezomib + cyclophosphamide + dexamethasone
arm group label: bortezomib + dexamethasone
arm group label: bortezomib + lenalidomide + dexamethasone
arm group label: bortezomib + pomalidomide + dexamethasone
arm group label: carfilzomib + dexamethasone
arm group label: carfilzomib + lenalidomide + dexamethasone
arm group label: carfilzomib + pomalidomide + dexamethasone
other name: Decadron
other name: Dexamethasone Intensol
other name: Dexpak Taperpak
intervention type: Dietary Supplement
intervention name: Ascorbic acid
description: Vitamin C will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + cyclophosphamide + ascorbic acid
other name: Vitamin C
intervention type: Drug
intervention name: PLD
description: Pegylated liposomal doxorubicin will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + PLD + dexamethasone
other name: ATI-0918
other name: doxorubicin hydrochloride liposome
other name: doxorubicin hydrochloride liposome injection
other name: liposomal adriamycin
other name: liposomal doxorubicin
other name: liposomal doxorubicin hydrochloride
other name: liposome-encapsulated doxorubicin
other name: pegylated doxorubicin HCl liposome
other name: Pegylated Liposomal Doxorubicin
other name: S-Liposomal Doxorubicin
other name: Stealth Liposomal Doxorubicin
other name: DOXIL
other name: Dox-SL
other name: Evacet
other name: LipoDox
intervention type: Drug
intervention name: Lenalidomide
description: Lenalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + lenalidomide + dexamethasone
arm group label: carfilzomib + lenalidomide + dexamethasone
other name: Revlimid
intervention type: Drug
intervention name: Pomalidomide
description: Pomalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
arm group label: bortezomib + pomalidomide + dexamethasone
arm group label: carfilzomib + pomalidomide + dexamethasone
other name: Pomalyst
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James R Berenson, MD
role: Principal Investigator
affiliation: James R. Berenson MD, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Ascorbic Acid
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Melphalan
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Lenalidomide
mesh term: Pomalidomide
mesh term: BB 1101