<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/NCT02185820</url>
  </required_header>
  <id_info>
    <org_study_id>EMN07/IST-CAR-538</org_study_id>
    <nct_id>NCT02185820</nct_id>
  </id_info>
  <brief_title>Phase I/II Study of Carfilzomib, Pomalidomide and Dexamethasone in Relapsed And/Or Refractory Multiple Myeloma Patients (CPD)</brief_title>
  <acronym>CPD</acronym>
  <official_title>A MULTICENTER, OPEN LABEL PHASE I/II STUDY OF CARFILZOMIB, POMALIDOMIDE AND DEXAMETHASONE IN RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (MM) PATIENTS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>European Myeloma Network</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Turin, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>European Myeloma Network</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This protocol is a phase I/II multicenter study designed to assess the safety and the&#xD;
      efficacy of the proposed combinations in relapsed and/or refractory Multiple Myeloma (MM)&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TREATMENT PERIOD Patients will start the salvage treatment with CPd, as soon as the screening&#xD;
      visits of the pre-treatment period have been terminated. Patients will receive 8 CPd cycles.&#xD;
&#xD;
      PHASE I&#xD;
&#xD;
      In the phase I part of the study, the following dose levels of pomalidomide will be studied&#xD;
      with a constant dose of dexamethasone and carfilzomib:&#xD;
&#xD;
      Level -1 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27 mg/m2&#xD;
      days 8, 15 in cycle 1, then for all subsequent doses 27 mg/m2 IV once daily on days 1, 8, 15&#xD;
      followed by 13-day rest period (day 16 through 28).&#xD;
&#xD;
      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,&#xD;
      15, 22 every 28 days. Level 0 (starting dose) Carfilzomib = 20 mg/m2 IV once daily on days 1&#xD;
      of cycle 1 only followed by 36 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 36&#xD;
      mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).&#xD;
&#xD;
      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,&#xD;
      15, 22 every 28 days. Level +1 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only&#xD;
      followed by 45 mg/ m2 days 8, 15 in cycle 1, then for all subsequent doses 45 mg/m2 IV once&#xD;
      daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).&#xD;
&#xD;
      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,&#xD;
      15, 22 every 28 days. Level +2 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only&#xD;
      followed by 56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 56 mg/m2 IV once&#xD;
      daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).&#xD;
&#xD;
      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,&#xD;
      15, 22 every 28 days. Patients will be observed during the first cycle of therapy for the&#xD;
      assessment of side effects and observation of DLTs.&#xD;
&#xD;
      Dose escalation will proceed as follows:&#xD;
&#xD;
      3 patients will be entered at dose level 0. If none of the 3 experience DLT, dose escalation&#xD;
      will continue. If one of three patients experience DLT, three additional patients will be&#xD;
      added to this cohort (max 6).&#xD;
&#xD;
      If two of three patients experience a DLT at any given dose, the MTD will have been exceeded&#xD;
      and the MTD will be the preceding dose at which &lt; one of 6 patients experienced a DLT.&#xD;
&#xD;
      If no further patients experience DLT (1 of 6) dose escalation will continue. If 2 patients&#xD;
      experience DLT (2 of 6) the MTD will have been exceeded and the MTD will be the previous dose&#xD;
      at which &lt;1 patient of 6 experienced DLT.&#xD;
&#xD;
      The phase I of the study will end once the MTD has been defined.&#xD;
&#xD;
      PHASE II The phase II of the study will start after the MTD has been defined in the phase I&#xD;
      of the study. The dose used to treat patients in the phase II will be the MTD defined in the&#xD;
      phase I of the study.&#xD;
&#xD;
      In the second part of the study, the MTD of the association CPd (or in absence of any MTD&#xD;
      observed) the doses of dose level 3 (maximum per protocol dose) will be administered to a&#xD;
      total of 45 consecutive patients in order to assess response rate and clinical efficacy.&#xD;
&#xD;
      THE PHASE 2 OF THE STUDY WILL START ONLY AFTER THE ANALYSIS OF THE PHASE 1 RESULTS AND THE&#xD;
      RELEVANT STUDY REPORT.&#xD;
&#xD;
      MANTEINANCE PERIOD&#xD;
&#xD;
      At the end of 8 courses, maintenance phase will start. Patients will receive:&#xD;
&#xD;
      Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days&#xD;
      cycles.&#xD;
&#xD;
      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,&#xD;
      15, 22. Patients will be stopped at PD or intolerance. For the maintenance period a&#xD;
      continuous assessment of the toxicity and tolerability profile of the CPd combination could&#xD;
      permit to the Investigators to continue the treatment using Pomalidomide or Carfilzomib alone&#xD;
      according to the dose modification plan.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2014</start_date>
  <completion_date type="Actual">January 2023</completion_date>
  <primary_completion_date type="Actual">July 2015</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>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>DLT</measure>
    <time_frame>1 year</time_frame>
    <description>The dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of carfilzomib, pomalidomide and dexamethasone (CPd) association.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Partial response</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the rate of partial response (PR) with the CPd association: a PR rate of 25% (p0) is considered not promising (H0) and a 45% (p1) as interesting.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicities</measure>
    <time_frame>3 years</time_frame>
    <description>Less than 30% of patients presenting the following toxicities: grade 4 neutropenia lasting &gt; 1 week, any grade 4 hematological toxicities except neutropenia, any &gt; grade 3 extra-hematologic toxicities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the progression-free survival (PFS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTP</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the time to progression (TTP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DFS</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the disease free survival (DFS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the duration of response (DOR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTNT</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the time to next therapy (TTNT).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the overall survival (OS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response and survival</measure>
    <time_frame>3 years</time_frame>
    <description>Determine whether tumor response and survival might significantly change in particular subgroups of patients defined on prognostic factors (β2-microglobulin, C-reactive protein (CRP), FISH).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment schedule for 8 cycles of induction:&#xD;
Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27/36/45/56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 27/36/45/56 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).&#xD;
Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days.&#xD;
Treatment schedule for maintenance until progression or intolerance:&#xD;
Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days cycles.&#xD;
Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age &gt; 18 years. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Patient&#xD;
        is, in the investigator(s) opinion, willing and able to comply with the protocol&#xD;
        requirements.&#xD;
&#xD;
        Patient has given voluntary written informed consent before performance of any&#xD;
        study-related procedure not part of normal medical care, with the understanding that&#xD;
        consent may be withdrawn by the patient at any time without prejudice to their future&#xD;
        medical care.&#xD;
&#xD;
        Female patient is either post-menopausal or surgically sterilized or willing to use an&#xD;
        acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device,&#xD;
        diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the&#xD;
        study.&#xD;
&#xD;
        Male patient agrees to use an acceptable method for contraception (i.e., condom or&#xD;
        abstinence) for the duration of the study.&#xD;
&#xD;
        Patients who are primary refractory or relapsed/refractory to Lenalidomide. Subjects must&#xD;
        have been received at least 2 consecutive cycles of a prior treatment that include&#xD;
        Lenalidomide alone or in combination.&#xD;
&#xD;
        Subject must be primary refractory or relapsed/refractory to Lenalidomide, defined as: 1)&#xD;
        never achieved any response better than progressive disease (PD) to any&#xD;
        Lenalidomide-containing regimen; 2) documented disease progression during or within 60 days&#xD;
        of completing their last myeloma Lenalidomide-containing regimen.&#xD;
&#xD;
        Both relapsed and/or refractory to Bortezomib and naive to Bortezomib patients can be&#xD;
        enrolled.&#xD;
&#xD;
        Patient has measurable disease, defined as follows: any quantifiable serum monoclonal&#xD;
        protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where&#xD;
        applicable, urine light-chain excretion of &gt;200 mg/24 hours. For patients with oligo or&#xD;
        non-secretory MM, it is required that they have measurable plasmacytoma &gt; 2 cm as&#xD;
        determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an&#xD;
        abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of&#xD;
        patients admitted to this study will be oligo- or non-secretory MM with free light chains&#xD;
        only in order to maximize interpretation of benefit results.&#xD;
&#xD;
        Patient has a Karnofsky performance status ≥60%. Patient has a life-expectancy &gt;3 months.&#xD;
&#xD;
        Patient has the following laboratory values within 14 days before Baseline (day 1 of the&#xD;
        Cycle 1, before study drug administration):&#xD;
&#xD;
        Platelet count ≥ 50 x 109/L (≥ 30 x 109/L if myeloma involvement in the bone marrow is &gt;&#xD;
        50%) within 14 days prior to drug administration).&#xD;
&#xD;
        Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (subjects may be receiving&#xD;
        red blood cell [RBC] transfusions in accordance with institutional guidelines).&#xD;
&#xD;
        Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors. Corrected&#xD;
        serum calcium ≤14 mg/dL (3.5 mmol/L) Alanine transaminase (ALT): ≤ 3.5 x the ULN. Total&#xD;
        bilirubin: ≤ 2 x the ULN. Calculated or measured creatinine clearance ≥ 45 mL/min.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Newly diagnosed myeloma patients. Patient with non-secretory MM, unless serum free light&#xD;
        chains are present and the ratio is abnormal.&#xD;
&#xD;
        Pregnant or lactating females. Major surgery within 21 days prior to enrollment. Acute&#xD;
        active infection requiring treatment (systemic antibiotics, antivirals, or antifungals)&#xD;
        within 14 days prior to enrolment.&#xD;
&#xD;
        Patient has active infectious hepatitis type A, B or C or HIV. Unstable angina or&#xD;
        myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart&#xD;
        failure, uncontrolled angina, history of severe coronary artery disease, severe&#xD;
        uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence&#xD;
        of acute ischemia or Grade 3 conduction system abnormalities unless subject has a&#xD;
        pacemaker.&#xD;
&#xD;
        Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.&#xD;
&#xD;
        Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to&#xD;
        enrollment.&#xD;
&#xD;
        Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize&#xD;
        carfilzomib).&#xD;
&#xD;
        Contraindication to any of the required concomitant drugs or supportive treatments,&#xD;
        including hypersensitivity to all anticoagulation and antiplatelet options, antiviral&#xD;
        drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment.&#xD;
&#xD;
        Subject with pleural effusions requiring thoracentesis or ascites requiring paracentesis&#xD;
        within 14 days prior to baseline.&#xD;
&#xD;
        Any other clinically significant medical disease or condition that, in the Investigator's&#xD;
        opinion, may interfere with protocol adherence or a subject's ability to give informed&#xD;
        consent.&#xD;
&#xD;
        Nonhematologic malignancy within the past 3 years with the exception of a) adequately&#xD;
        treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in&#xD;
        situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable&#xD;
        prostate-specific antigen levels; or d) cancer considered cured by surgical resection or&#xD;
        unlikely to impact survival during the duration of the study, such as localized&#xD;
        transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.&#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>Sara Bringhen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AOU Città della Salute e della Scienza di Torino</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dipartimento di Biotecnologie Molecolari e Scienze per la Salute</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple myeloma</keyword>
  <keyword>Relapsed and/or refractory</keyword>
  <keyword>CPD</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>Dexamethasone</mesh_term>
    <mesh_term>Pomalidomide</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/NCT02185820
org study id: EMN07/IST-CAR-538
nct id: NCT02185820
lead sponsor: 
collaborator: 
has dmc: Yes
This protocol is a phase I/II multicenter study designed to assess the safety and the
      efficacy of the proposed combinations in relapsed and/or refractory Multiple Myeloma (MM)
      patients.
TREATMENT PERIOD Patients will start the salvage treatment with CPd, as soon as the screening
      visits of the pre-treatment period have been terminated. Patients will receive 8 CPd cycles.

      PHASE I

      In the phase I part of the study, the following dose levels of pomalidomide will be studied
      with a constant dose of dexamethasone and carfilzomib:

      Level -1 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27 mg/m2
      days 8, 15 in cycle 1, then for all subsequent doses 27 mg/m2 IV once daily on days 1, 8, 15
      followed by 13-day rest period (day 16 through 28).

      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,
      15, 22 every 28 days. Level 0 (starting dose) Carfilzomib = 20 mg/m2 IV once daily on days 1
      of cycle 1 only followed by 36 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 36
      mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).

      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,
      15, 22 every 28 days. Level +1 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only
      followed by 45 mg/ m2 days 8, 15 in cycle 1, then for all subsequent doses 45 mg/m2 IV once
      daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).

      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,
      15, 22 every 28 days. Level +2 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only
      followed by 56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 56 mg/m2 IV once
      daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).

      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,
      15, 22 every 28 days. Patients will be observed during the first cycle of therapy for the
      assessment of side effects and observation of DLTs.

      Dose escalation will proceed as follows:

      3 patients will be entered at dose level 0. If none of the 3 experience DLT, dose escalation
      will continue. If one of three patients experience DLT, three additional patients will be
      added to this cohort (max 6).

      If two of three patients experience a DLT at any given dose, the MTD will have been exceeded
      and the MTD will be the preceding dose at which < one of 6 patients experienced a DLT.

      If no further patients experience DLT (1 of 6) dose escalation will continue. If 2 patients
      experience DLT (2 of 6) the MTD will have been exceeded and the MTD will be the previous dose
      at which <1 patient of 6 experienced DLT.

      The phase I of the study will end once the MTD has been defined.

      PHASE II The phase II of the study will start after the MTD has been defined in the phase I
      of the study. The dose used to treat patients in the phase II will be the MTD defined in the
      phase I of the study.

      In the second part of the study, the MTD of the association CPd (or in absence of any MTD
      observed) the doses of dose level 3 (maximum per protocol dose) will be administered to a
      total of 45 consecutive patients in order to assess response rate and clinical efficacy.

      THE PHASE 2 OF THE STUDY WILL START ONLY AFTER THE ANALYSIS OF THE PHASE 1 RESULTS AND THE
      RELEVANT STUDY REPORT.

      MANTEINANCE PERIOD

      At the end of 8 courses, maintenance phase will start. Patients will receive:

      Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days
      cycles.

      Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8,
      15, 22. Patients will be stopped at PD or intolerance. For the maintenance period a
      continuous assessment of the toxicity and tolerability profile of the CPd combination could
      permit to the Investigators to continue the treatment using Pomalidomide or Carfilzomib alone
      according to the dose modification plan.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLT
time frame: 1 year
description: The dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of carfilzomib, pomalidomide and dexamethasone (CPd) association.
measure: Partial response
time frame: 3 years
description: Determine the rate of partial response (PR) with the CPd association: a PR rate of 25% (p0) is considered not promising (H0) and a 45% (p1) as interesting.
measure: Toxicities
time frame: 3 years
description: Less than 30% of patients presenting the following toxicities: grade 4 neutropenia lasting > 1 week, any grade 4 hematological toxicities except neutropenia, any > grade 3 extra-hematologic toxicities.
measure: PFS
time frame: 3 years
description: Determine the progression-free survival (PFS).
measure: TTP
time frame: 3 years
description: Determine the time to progression (TTP).
measure: DFS
time frame: 3 years
description: Determine the disease free survival (DFS).
measure: DOR
time frame: 3 years
description: Determine the duration of response (DOR).
measure: TTNT
time frame: 3 years
description: Determine the time to next therapy (TTNT).
measure: OS
time frame: 3 years
description: Determine the overall survival (OS).
measure: Tumor response and survival
time frame: 3 years
description: Determine whether tumor response and survival might significantly change in particular subgroups of patients defined on prognostic factors (β2-microglobulin, C-reactive protein (CRP), FISH).
arm group label: 1
arm group type: Experimental
description: Treatment schedule for 8 cycles of induction:
Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27/36/45/56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 27/36/45/56 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28).
Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days.
Treatment schedule for maintenance until progression or intolerance:
Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days cycles.
Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22.
intervention type: Drug
intervention name: Carfilzomib
arm group label: 1
intervention type: Drug
intervention name: Pomalidomide
arm group label: 1
intervention type: Drug
intervention name: Dexamethasone
arm group label: 1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sara Bringhen, MD
role: Principal Investigator
affiliation: AOU Città della Salute e della Scienza di Torino
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Pomalidomide