<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/NCT01660750</url>
  </required_header>
  <id_info>
    <org_study_id>AMyC 11-MM-01</org_study_id>
    <secondary_id>CAR-IST-520</secondary_id>
    <nct_id>NCT01660750</nct_id>
  </id_info>
  <brief_title>A Safety Study of Carfilzomib, Cyclophosphamide &amp; Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma</brief_title>
  <acronym>11-MM-01</acronym>
  <official_title>A Multi-Center Phase Ib, Open-Label, Dose-Finding Pilot Study to Evaluate the Combination of Carfilzomib and Cyclophosphamide With Dexamethasone Prior to ASCT in Patients With Transplant Eligible Newly Diagnosed Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Criterium, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Criterium, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated&#xD;
      dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex)&#xD;
      prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant&#xD;
      eligible multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated&#xD;
      dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex)&#xD;
      prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant&#xD;
      eligible multiple myeloma. The study will also explore the efficacy of Car-Cy-Dex including&#xD;
      overall response after induction therapy, overall response at 3 and 6 months post ASCT, and&#xD;
      time to progression, progression free survival, and time to next therapy if it occurs within&#xD;
      6 months post ASCT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>Phase 1</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>Adverse Events as a measure of safety and tolerability</measure>
    <time_frame>Throughout treatment, estimated to be 4-6 months per patients</time_frame>
    <description>Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response after induction therapy</measure>
    <time_frame>Every 28 days during induction therapy, estimated to be 4-6 months</time_frame>
    <description>Overall response (PR, VGPR, CR, sCR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response post ASCT</measure>
    <time_frame>3 and 6 months post ASCT</time_frame>
    <description>Overall Response (PR, VGPR, CR, sCR) at 3 and 6 months post ASCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>Througout treatment and 3 and 6 months post ASCT</time_frame>
    <description>Time to progression will be noted if it occurs within 6 months post ASCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>up to 6 months post ASCT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Next Therapy</measure>
    <time_frame>up to 6 months post ASCT</time_frame>
    <description>Time to Next Therapy if occurs within 6 months post ASCT</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Carfilzomib, Cyclophosphamide, Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days</description>
    <arm_group_label>Carfilzomib, Cyclophosphamide, Dexamethasone</arm_group_label>
    <other_name>PR-171</other_name>
    <other_name>Kyprolis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>PO on days 1, 8, and 15 every 28 days</description>
    <arm_group_label>Carfilzomib, Cyclophosphamide, Dexamethasone</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.</description>
    <arm_group_label>Carfilzomib, Cyclophosphamide, Dexamethasone</arm_group_label>
    <other_name>Decadron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cytopathologically or histologically confirmed diagnosis of MM&#xD;
&#xD;
          -  Measurable disease, as indicated by one or more of the following:&#xD;
&#xD;
          -  Serum M-protein ≥ 1.0 g/dL&#xD;
&#xD;
          -  Urine Bence Jones protein ≥ 200 mg/24 hr&#xD;
&#xD;
          -  Elevated Free Light Chain as per the International Myeloma Working Group (IMWG)&#xD;
             criteria&#xD;
&#xD;
          -  Males and females ≥ 18 years of age&#xD;
&#xD;
          -  Life expectancy of more than 5 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2&#xD;
&#xD;
          -  Adequate hepatic function, with bilirubin &lt; 2 times the upper limit of normal (ULN),&#xD;
             and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 3.5 times&#xD;
             ULN&#xD;
&#xD;
          -  Serum Creatinine Clearance(CrCl) ≥ 30 mL/min, either measured or calculated using a&#xD;
             standard formula (e.g. Cockcroft and Gault)&#xD;
&#xD;
          -  Additional Laboratory Requirements&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥1.0 x 109/L&#xD;
&#xD;
          -  Hemoglobin ≥8 g/dL [transfusion permitted]&#xD;
&#xD;
          -  Platelet count ≥50.0 x 109/L&#xD;
&#xD;
          -  Screening ANC should be independent of granulocyte-and granulocyte/macrophage colony&#xD;
             stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated&#xD;
             G-CSF for at least 2 weeks&#xD;
&#xD;
          -  Patients may receive RBC or platelet transfusions, if clinically indicated, in&#xD;
             accordance with institutional guidelines&#xD;
&#xD;
          -  Written informed consent in accordance with federal, local, and institutional&#xD;
             guidelines&#xD;
&#xD;
          -  Patients must agree to practice contraception&#xD;
&#xD;
          -  Male patients must agree not to donate semen or sperm.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with non-secretory or hyposecretory MM&#xD;
&#xD;
          -  Prior treatment for MM (prior radiation therapy or dexamethasone up to 160 mg for&#xD;
             spinal cord compression is allowed. Other limited field radiation involving ≤ 1/3 of&#xD;
             the pelvic area is also allowed)&#xD;
&#xD;
          -  Plasma cell leukemia&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Major surgery within 21 days prior to first dose&#xD;
&#xD;
          -  Congestive heart failure (CHF) (New York Heart Association class III to IV),&#xD;
             symptomatic ischemia, conduction abnormalities uncontrolled by conventional&#xD;
             intervention or myocardial infarction in the previous six months&#xD;
&#xD;
          -  Acute active infection requiring systemic antibiotics, antivirals, or antifungals&#xD;
             within 14 days prior to first dose&#xD;
&#xD;
          -  Patients receiving active treatment or intervention for any other malignancy or&#xD;
             patients who, at the Investigator's discretion, may require active treatment or&#xD;
             intervention for any other malignancy within 8 months of starting study treatment.&#xD;
&#xD;
          -  Serious psychiatric or medical conditions that could interfere with treatment&#xD;
&#xD;
          -  Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the&#xD;
             first dose and/or within 14 days before study treatment&#xD;
&#xD;
          -  Contraindication to any of the required concomitant drugs, including antiviral (e.g.&#xD;
             Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in&#xD;
             a dose equivalent to dexamethasone ≥ 1.5 mg/day or prednisone ≥ 10 mg/day. (Steroid&#xD;
             use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.)&#xD;
&#xD;
          -  Patients in whom the required program of oral and IV fluid hydration is&#xD;
             contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment&#xD;
&#xD;
          -  Patients with primary systemic amyloidosis.&#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>Jatin Shah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AMyC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brian GM Durie, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AMyC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</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>University of Massachusettes Memorial</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>October 16, 2017</last_update_submitted>
  <last_update_submitted_qc>October 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>newly diagnosed multiple myeloma</keyword>
  <keyword>transplant eligible multiple myeloma</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>Cyclophosphamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT01660750
org study id: AMyC 11-MM-01
secondary id: CAR-IST-520
nct id: NCT01660750
lead sponsor: 
collaborator: 
has dmc: No
This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated
      dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex)
      prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant
      eligible multiple myeloma.
This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated
      dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex)
      prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant
      eligible multiple myeloma. The study will also explore the efficacy of Car-Cy-Dex including
      overall response after induction therapy, overall response at 3 and 6 months post ASCT, and
      time to progression, progression free survival, and time to next therapy if it occurs within
      6 months post ASCT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events as a measure of safety and tolerability
time frame: Throughout treatment, estimated to be 4-6 months per patients
description: Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
measure: Overall Response after induction therapy
time frame: Every 28 days during induction therapy, estimated to be 4-6 months
description: Overall response (PR, VGPR, CR, sCR)
measure: Overall Response post ASCT
time frame: 3 and 6 months post ASCT
description: Overall Response (PR, VGPR, CR, sCR) at 3 and 6 months post ASCT.
measure: Time to Progression
time frame: Througout treatment and 3 and 6 months post ASCT
description: Time to progression will be noted if it occurs within 6 months post ASCT.
measure: Progression Free Survival
time frame: up to 6 months post ASCT
measure: Time to Next Therapy
time frame: up to 6 months post ASCT
description: Time to Next Therapy if occurs within 6 months post ASCT
arm group label: Carfilzomib, Cyclophosphamide, Dexamethasone
arm group type: Experimental
description: All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.
intervention type: Drug
intervention name: Carfilzomib
description: IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
arm group label: Carfilzomib, Cyclophosphamide, Dexamethasone
other name: PR-171
other name: Kyprolis
intervention type: Drug
intervention name: Cyclophosphamide
description: PO on days 1, 8, and 15 every 28 days
arm group label: Carfilzomib, Cyclophosphamide, Dexamethasone
other name: Cytoxan
intervention type: Drug
intervention name: Dexamethasone
description: 40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.
arm group label: Carfilzomib, Cyclophosphamide, Dexamethasone
other name: Decadron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jatin Shah, MD
role: Principal Investigator
affiliation: AMyC
last name: Brian GM Durie, MD
role: Principal Investigator
affiliation: AMyC
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Cyclophosphamide
sharing ipd: Undecided