<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/NCT01665794</url>
  </required_header>
  <id_info>
    <org_study_id>12-1088</org_study_id>
    <secondary_id>NCI-2012-01168</secondary_id>
    <nct_id>NCT01665794</nct_id>
  </id_info>
  <brief_title>Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Pomalidomide, Dexamethasone, and Carfilzomib (PdC) in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Multiple Myeloma Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will investigate the effects of adding carfilzomib to the combination of&#xD;
      pomalidomide and dexamethasone in sequential dose escalation cohorts in patients with&#xD;
      relapsed or refractory multiple myeloma. This portion of the study is complete.&#xD;
&#xD;
      This study will also investigate the effects of adding daratumumab to the combination of&#xD;
      carfilzomib, pomalidomide and dexamethasone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients receive carfilzomib, pomalidomide, and dexamethasone in 28 days treatment cycles.&#xD;
      Study treatment continues for as long a their myeloma does not worsen and they do not have&#xD;
      unacceptable side effects. After completion of study treatment, patients are followed for up&#xD;
      to 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 13, 2012</start_date>
  <completion_date type="Anticipated">November 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2024</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) of carfilzomib when administered in combination with pomalidomide and dexamethasone</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Partial response rate after 4 courses according to International Myeloma Working Group (IMWG) criteria</measure>
    <time_frame>4 months</time_frame>
    <description>The proportion and exact 95% binomial confidence interval for the response rate will be reported adjusted for the two-stage design of this trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rates of carfilzomib, pomalidomide, dexamethasone, and daratumumab dosing according to International Myeloma Working Group (IMWG) criteria</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Defined as at least a partial response to therapy, will be reported along with its exact 95% binomial confidence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Estimated using the product-limit method of Kaplan and Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>From the date of the clinical examination which confirmed the response, until the date of disease progression, or censoring at the date of last clinical follow-up up to 2 years</time_frame>
    <description>Assessed conditional upon achieving at least a partial response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>From the date of first therapy until the date of documented disease progression or death up to 2 years</time_frame>
    <description>Estimated using the product-limit method of Kaplan and Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Estimated using the product-limit method of Kaplan and Meier.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">101</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>PdC Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PdC + Dara Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive carfilzomib, pomalidomide, dexamethasone, and daratumumab at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>Pomalidomide taken orally at assigned dose.</description>
    <arm_group_label>PdC + Dara Group</arm_group_label>
    <arm_group_label>PdC Group</arm_group_label>
    <other_name>CC-4047</other_name>
    <other_name>Pomalyst(R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Carfilzomib given by intravenous (IV) infusion at assigned dose.</description>
    <arm_group_label>PdC + Dara Group</arm_group_label>
    <arm_group_label>PdC Group</arm_group_label>
    <other_name>Kyprolis (R)</other_name>
    <other_name>PR-171</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dexamethasone</intervention_name>
    <description>Dexamethasone taken orally of given by IV infusion.</description>
    <arm_group_label>PdC + Dara Group</arm_group_label>
    <arm_group_label>PdC Group</arm_group_label>
    <other_name>Aeroseb-Dex</other_name>
    <other_name>Decaderm</other_name>
    <other_name>Decadron</other_name>
    <other_name>DM</other_name>
    <other_name>DXM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>Daratumumab given by intravenous (IV) infusion at assigned dose.</description>
    <arm_group_label>PdC + Dara Group</arm_group_label>
    <other_name>Daralex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Relapsed and relapsed/refractory multiple myeloma requiring systemic therapy&#xD;
&#xD;
          -  Failed at least one prior treatment for multiple myeloma (must have received&#xD;
             lenalidomide)&#xD;
&#xD;
               -  To be enrolled as second line therapy: Must be refractory to lenalidomide&#xD;
                  (progression on therapy or within 60 days of lenalidomide dosing)&#xD;
&#xD;
          -  Measurable disease, as indicated by one or more of the following:&#xD;
&#xD;
               -  Serum M-protein &gt;= 0.5 g/dL&#xD;
&#xD;
               -  Urine M-protein &gt;= 200 mg/24 hours&#xD;
&#xD;
               -  If serum protein electrophoresis is felt to be unreliable for routine M-protein&#xD;
                  measurement, then quantitative immunoglobulin levels are acceptable&#xD;
&#xD;
               -  Involved serum free light chains ≥ 10 mg/dL (free light change ratio must be&#xD;
                  abnormal)&#xD;
&#xD;
          -  Aged 18 years or older&#xD;
&#xD;
          -  Life expectancy of more than 3 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Adequate Liver Function&#xD;
&#xD;
               -  Bilirubin &lt; 1.5 times the upper limit of normal (ULN)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) &lt; 2.5 times ULN&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) &lt; 2.5 times ULN&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1.0 x 10^9/L&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 g/dL&#xD;
&#xD;
          -  Platelet count &gt;= 75 x 10^9/L (should be independent of platelet transfusions for at&#xD;
             least 2 weeks)&#xD;
&#xD;
          -  Calculated or measured creatinine clearance of &gt;= 30 mL/minute&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Negative pregnancy test (for women of childbearing potential) within 10-14 days of&#xD;
             starting study treatment and again within 24 hours of first pomalidomide dose&#xD;
&#xD;
          -  Must agree to practice abstinence or use two acceptable methods of birth control&#xD;
&#xD;
          -  Men must agree to use latex condom during sexual contact with women of childbearing&#xD;
             potential (even if post vasectomy)&#xD;
&#xD;
          -  Must agree to adhere to all study requirements, visit schedule, outpatient treatment,&#xD;
             required concomitant medications, and laboratory monitoring&#xD;
&#xD;
          -  Must register to mandatory POMALYST REMS™ program and be willing and able to comply&#xD;
             with the requirements of the POMALYST REMS™ program&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients for whom there is the prospect of stem cell transplantation in the next 6&#xD;
             months in the treatment plan are excluded&#xD;
&#xD;
          -  POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and&#xD;
             skin changes)&#xD;
&#xD;
          -  Plasma cell leukemia&#xD;
&#xD;
          -  Waldenström's macroglobulinemia or immunoglobulin M (IgM) myeloma&#xD;
&#xD;
          -  Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of&#xD;
             protocol treatment (localized radiotherapy to a single site at least 1 week before&#xD;
             start is permissible)&#xD;
&#xD;
          -  Participation in an investigational therapeutic study within 3 weeks or within 5 drug&#xD;
             half lives (t1/2) prior to first dose, whichever time is greater&#xD;
&#xD;
          -  Patients known to be refractory to any proteasome inhibitor other than bortezomib or&#xD;
             carfilzomib&#xD;
&#xD;
          -  Pregnant or lactating&#xD;
&#xD;
          -  History of allergy to mannitol or prior hypersensitivity to thalidomide, lenalidomide&#xD;
             or pomalidomide&#xD;
&#xD;
          -  Major surgery within 3 weeks prior to first dose,&#xD;
&#xD;
          -  Prior peripheral stem cell transplant within 12 weeks of study enrollment&#xD;
&#xD;
          -  Has received any anti-cancer therapy including chemotherapy, immunotherapy,&#xD;
             radiotherapy, hormonal (with the exception of hormones for thyroid conditions or&#xD;
             estrogen replacement therapy [ERT]), or any investigational therapy within 21 days of&#xD;
             enrollment&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment, New York Heart Associate&#xD;
             (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled&#xD;
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active&#xD;
             conduction system abnormalities&#xD;
&#xD;
          -  Uncontrolled hypertension or diabetes&#xD;
&#xD;
          -  Acute active infection requiring systemic antibiotics, antivirals, or anti fungals&#xD;
             within two weeks prior to first dose&#xD;
&#xD;
          -  Known or suspected human immunodeficiency (HIV) infection, known HIV seropositivity&#xD;
&#xD;
          -  Active hepatitis A, B, or C infection&#xD;
&#xD;
          -  Non-hematologic malignancy within the past 3 years except adequately treated basal&#xD;
             cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix or&#xD;
             breast, prostate cancer &lt; Gleason grade 6 with stable prostate specific antigen levels&#xD;
             or cancer considered cured by surgical resection alone&#xD;
&#xD;
          -  Any 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;
          -  Significant neuropathy (grades 3-4, or grade 2 with pain) at the time of the first&#xD;
             dose and/or within 14 days before enrollment&#xD;
&#xD;
          -  Contraindications to any of the required concomitant drugs, including proton-pump&#xD;
             inhibitor (eg, lansoprazole), enteric-coated aspirin, allopurinol or if a history of&#xD;
             prior thrombotic disease, warfarin or low molecular weight heparin&#xD;
&#xD;
          -  Subjects in whom the required program of PO and IV fluid hydration is contraindicated,&#xD;
             eg, due to pre-existing pulmonary, cardiac, or renal impairment&#xD;
&#xD;
          -  Subjects with known or suspected amyloidosis of any organ&#xD;
&#xD;
          -  Subjects with pleural effusions requiring thoracentesis or ascites requiring&#xD;
             paracentesis&#xD;
&#xD;
          -  Prior exposure to daratumumab&#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>Andrzej Jakubowiak</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago Comprehensive Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Cancer Clinical Trials Office</last_name>
    <phone>1-855-702-8222</phone>
    <email>cancerclinicaltrials@bsd.uchicago.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1470</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrzej J. Jakubowiak</last_name>
      <phone>773-834-1592</phone>
      <email>ajakubowiak@medicine.bsd.uchicago.edu</email>
    </contact>
    <investigator>
      <last_name>Andrzej J. Jakubowiak</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Wayne State University - Karmonos Cancer Center</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jesus Berdeja, MD</last_name>
      <phone>615-329-7274</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Health Network - Princess Margaret Cancer Center</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>MISG 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <last_update_submitted>April 26, 2023</last_update_submitted>
  <last_update_submitted_qc>April 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2023</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>Daratumumab</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/NCT01665794
org study id: 12-1088
secondary id: NCI-2012-01168
nct id: NCT01665794
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The study will investigate the effects of adding carfilzomib to the combination of
      pomalidomide and dexamethasone in sequential dose escalation cohorts in patients with
      relapsed or refractory multiple myeloma. This portion of the study is complete.

      This study will also investigate the effects of adding daratumumab to the combination of
      carfilzomib, pomalidomide and dexamethasone.
Patients receive carfilzomib, pomalidomide, and dexamethasone in 28 days treatment cycles.
      Study treatment continues for as long a their myeloma does not worsen and they do not have
      unacceptable side effects. After completion of study treatment, patients are followed for up
      to 2 years.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) of carfilzomib when administered in combination with pomalidomide and dexamethasone
time frame: 28 days
measure: Partial response rate after 4 courses according to International Myeloma Working Group (IMWG) criteria
time frame: 4 months
description: The proportion and exact 95% binomial confidence interval for the response rate will be reported adjusted for the two-stage design of this trial.
measure: Response rates of carfilzomib, pomalidomide, dexamethasone, and daratumumab dosing according to International Myeloma Working Group (IMWG) criteria
time frame: 4 months
measure: Overall response rate
time frame: Up to 2 years
description: Defined as at least a partial response to therapy, will be reported along with its exact 95% binomial confidence
measure: Time to progression
time frame: Up to 2 years
description: Estimated using the product-limit method of Kaplan and Meier.
measure: Duration of response
time frame: From the date of the clinical examination which confirmed the response, until the date of disease progression, or censoring at the date of last clinical follow-up up to 2 years
description: Assessed conditional upon achieving at least a partial response.
measure: Progression-free survival
time frame: From the date of first therapy until the date of documented disease progression or death up to 2 years
description: Estimated using the product-limit method of Kaplan and Meier.
measure: Overall survival
time frame: Up to 2 years
description: Estimated using the product-limit method of Kaplan and Meier.
arm group label: PdC Group
arm group type: Experimental
description: Patients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
arm group label: PdC + Dara Group
arm group type: Experimental
description: Patients receive carfilzomib, pomalidomide, dexamethasone, and daratumumab at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Pomalidomide
description: Pomalidomide taken orally at assigned dose.
arm group label: PdC + Dara Group
arm group label: PdC Group
other name: CC-4047
other name: Pomalyst(R)
intervention type: Drug
intervention name: Carfilzomib
description: Carfilzomib given by intravenous (IV) infusion at assigned dose.
arm group label: PdC + Dara Group
arm group label: PdC Group
other name: Kyprolis (R)
other name: PR-171
intervention type: Drug
intervention name: dexamethasone
description: Dexamethasone taken orally of given by IV infusion.
arm group label: PdC + Dara Group
arm group label: PdC Group
other name: Aeroseb-Dex
other name: Decaderm
other name: Decadron
other name: DM
other name: DXM
intervention type: Drug
intervention name: Daratumumab
description: Daratumumab given by intravenous (IV) infusion at assigned dose.
arm group label: PdC + Dara Group
other name: Daralex
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrzej Jakubowiak
role: Principal Investigator
affiliation: University of Chicago Comprehensive Cancer Center
last name: Cancer Clinical Trials Office
phone: 1-855-702-8222
email: cancerclinicaltrials@bsd.uchicago.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Daratumumab
mesh term: Pomalidomide