<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/NCT02220608</url>
  </required_header>
  <id_info>
    <org_study_id>201412026</org_study_id>
    <secondary_id>1KL2TR002346-01</secondary_id>
    <nct_id>NCT02220608</nct_id>
  </id_info>
  <brief_title>Phase I Study of Bortezomib With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma</brief_title>
  <official_title>A Phase I Study of the Safety and Feasibility of Bortezomib in Combination With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to determine the highest dose of a drug called&#xD;
      bortezomib that can be given with a drug called G-CSF before stem cell collection to help in&#xD;
      the mobilization of stem cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this phase I study is to define the maximum tolerated dose of bortezomib and&#xD;
      its mobilization effects when given with G-CSF for stem cell mobilization in multiple myeloma&#xD;
      patients. We hypothesize that bortezomib, in addition to increasing the number of mobilized&#xD;
      stem cells, will optimize final apheresis product by decreasing myeloma cell contamination.&#xD;
      Therefore, all multiple myeloma patients rather than multiple myeloma patients with G-CSF&#xD;
      mobilization failure will be the target of this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2015</start_date>
  <completion_date type="Actual">November 30, 2016</completion_date>
  <primary_completion_date type="Actual">July 31, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) of bortezomib when given with G-CSF</measure>
    <time_frame>Approximately 12 months (completion of all patients on trial)</time_frame>
    <description>The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first 28 days after administration of the first dose of bortezomib and before auto-HSCT. Dose escalations will proceed until the MTD has been reached.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm 1: Dose Level 1 (Bortezomib &amp; G-CSF)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>G-CSF will be administered daily for 5 days (Days 1-5). On Day 4 at approximately 1800 hours, bortezomib will be administered. Apheresis will begin on Day 5 either 15 or 18 hours following Day 4 bortezomib dose; 20L of peripheral blood will be processed with a cumulative target collection goal of &gt; 6.0x106 CD34+cells/kg. If the target collection goal is not met after one apheresis procedures, up to three additional days of G-CSF and apheresis may be repeated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: Dose Level 2 (Bortezomib &amp; G-CSF)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>G-CSF will be administered daily for 5 days (Days 1-5). On Day 4 at approximately 1800 hours, bortezomib will be administered. Apheresis will begin on Day 5 either 15 or 18 hours following Day 4 bortezomib dose; 20L of peripheral blood will be processed with a cumulative target collection goal of &gt; 6.0x106 CD34+cells/kg. If the target collection goal is not met after one apheresis procedures, up to three additional days of G-CSF and apheresis may be repeated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <arm_group_label>Arm 1: Dose Level 1 (Bortezomib &amp; G-CSF)</arm_group_label>
    <arm_group_label>Arm 2: Dose Level 2 (Bortezomib &amp; G-CSF)</arm_group_label>
    <other_name>Velcade</other_name>
    <other_name>LDP 341</other_name>
    <other_name>MLN341</other_name>
    <other_name>PS-341</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>G-CSF</intervention_name>
    <arm_group_label>Arm 1: Dose Level 1 (Bortezomib &amp; G-CSF)</arm_group_label>
    <arm_group_label>Arm 2: Dose Level 2 (Bortezomib &amp; G-CSF)</arm_group_label>
    <other_name>Neupogen</other_name>
    <other_name>filgrastim XM02</other_name>
    <other_name>granulocyte colony-stimulating factor</other_name>
    <other_name>Recombinant Methionyl Human Granulocyte Colony Stimulating Factor</other_name>
    <other_name>tbo-filgrastim</other_name>
    <other_name>tevagrastim</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis of multiple myeloma.&#xD;
&#xD;
          -  Eligible for autologous transplantation.&#xD;
&#xD;
          -  Received at least two cycles of any regimen as initial systemic therapy for multiple&#xD;
             myeloma and are within 2-12 months of the first dose of initial therapy.&#xD;
&#xD;
          -  At least 18 years of age.&#xD;
&#xD;
          -  ECOG performance status ≤ 2&#xD;
&#xD;
          -  Normal bone marrow and organ function as defined below:&#xD;
&#xD;
               -  Platelets ≥ 50,000/mm3&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count ≥1,000/mm3&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x IULN&#xD;
&#xD;
               -  Measured or calculated creatinine clearance ≥ 30 mL/min&#xD;
&#xD;
          -  Female patients who:&#xD;
&#xD;
               -  are postmenopausal for at least 1 year before the screening visit OR&#xD;
&#xD;
               -  are surgically sterile OR&#xD;
&#xD;
               -  Women of childbearing potential and men must agree to practice 2 effective&#xD;
                  methods of contraception prior to study entry, for the duration of study&#xD;
                  participation, and for 30 days after the last dose of study treatment. Should a&#xD;
                  woman become pregnant or suspect she is pregnant while participating in this&#xD;
                  study, she must inform her treating physician immediately.&#xD;
&#xD;
          -  Ability to understand and willingness to sign an IRB approved written informed consent&#xD;
             document (or that of legally authorized representative, if applicable).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous stem cell collection or transplantation (autologous or allogeneic).&#xD;
&#xD;
          -  Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior&#xD;
             to auto-HSCT.&#xD;
&#xD;
          -  Diagnosis of plasma cell leukemia.&#xD;
&#xD;
          -  Concurrent hematologic or non-hematologic malignancy requiring treatment (other than&#xD;
             multiple myeloma or secondary amyloidosis).&#xD;
&#xD;
          -  Radiation therapy within 3 weeks prior to enrollment.&#xD;
&#xD;
          -  Grade 2 or higher peripheral neuropathy.&#xD;
&#xD;
          -  Known hypersensitivity to any of the following: bortezomib, boron, mannitol.&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment or New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe&#xD;
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute&#xD;
             ischemia or active conduction system abnormalities&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, or serious medical or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirements.&#xD;
&#xD;
          -  Female patients who are pregnant and/or breastfeeding. Patient must have a negative&#xD;
             serum pregnancy test within 14 days of study entry.&#xD;
&#xD;
          -  Known HIV-positivity. These patients are at increased risk of lethal infections when&#xD;
             treated with marrow-suppressive therapy. Appropriate studies will be undertaken in&#xD;
             patients with HIV-positivity when indicated.&#xD;
&#xD;
          -  Participation in clinical trials with other investigational agents not included in&#xD;
             this trial, within 14 days of the start of the trial and throughout the duration of&#xD;
             the trial&#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>Armin Ghobadi, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <reference>
    <citation>Ghobadi A, Holt M, Ritchey J et al. The effect of Bortezomib (B) Alone or in Combination with Other Agents for Stem Cell Mobilization in Mice. Blood (ASH Annual Meeting Abstracts), Nov 2012; 120: 583</citation>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>January 4, 2018</last_update_submitted>
  <last_update_submitted_qc>January 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>G-CSF</keyword>
  <keyword>Bortezomib</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>Bortezomib</mesh_term>
    <mesh_term>Lenograstim</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT02220608
org study id: 201412026
secondary id: 1KL2TR002346-01
nct id: NCT02220608
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research study is to determine the highest dose of a drug called
      bortezomib that can be given with a drug called G-CSF before stem cell collection to help in
      the mobilization of stem cells.
The purpose of this phase I study is to define the maximum tolerated dose of bortezomib and
      its mobilization effects when given with G-CSF for stem cell mobilization in multiple myeloma
      patients. We hypothesize that bortezomib, in addition to increasing the number of mobilized
      stem cells, will optimize final apheresis product by decreasing myeloma cell contamination.
      Therefore, all multiple myeloma patients rather than multiple myeloma patients with G-CSF
      mobilization failure will be the target of this study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) of bortezomib when given with G-CSF
time frame: Approximately 12 months (completion of all patients on trial)
description: The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first 28 days after administration of the first dose of bortezomib and before auto-HSCT. Dose escalations will proceed until the MTD has been reached.
arm group label: Arm 1: Dose Level 1 (Bortezomib & G-CSF)
arm group type: Experimental
description: G-CSF will be administered daily for 5 days (Days 1-5). On Day 4 at approximately 1800 hours, bortezomib will be administered. Apheresis will begin on Day 5 either 15 or 18 hours following Day 4 bortezomib dose; 20L of peripheral blood will be processed with a cumulative target collection goal of > 6.0x106 CD34+cells/kg. If the target collection goal is not met after one apheresis procedures, up to three additional days of G-CSF and apheresis may be repeated.
arm group label: Arm 2: Dose Level 2 (Bortezomib & G-CSF)
arm group type: Experimental
description: G-CSF will be administered daily for 5 days (Days 1-5). On Day 4 at approximately 1800 hours, bortezomib will be administered. Apheresis will begin on Day 5 either 15 or 18 hours following Day 4 bortezomib dose; 20L of peripheral blood will be processed with a cumulative target collection goal of > 6.0x106 CD34+cells/kg. If the target collection goal is not met after one apheresis procedures, up to three additional days of G-CSF and apheresis may be repeated.
intervention type: Biological
intervention name: Bortezomib
arm group label: Arm 1: Dose Level 1 (Bortezomib & G-CSF)
arm group label: Arm 2: Dose Level 2 (Bortezomib & G-CSF)
other name: Velcade
other name: LDP 341
other name: MLN341
other name: PS-341
intervention type: Drug
intervention name: G-CSF
arm group label: Arm 1: Dose Level 1 (Bortezomib & G-CSF)
arm group label: Arm 2: Dose Level 2 (Bortezomib & G-CSF)
other name: Neupogen
other name: filgrastim XM02
other name: granulocyte colony-stimulating factor
other name: Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
other name: tbo-filgrastim
other name: tevagrastim
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Armin Ghobadi, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
citation: Ghobadi A, Holt M, Ritchey J et al. The effect of Bortezomib (B) Alone or in Combination with Other Agents for Stem Cell Mobilization in Mice. Blood (ASH Annual Meeting Abstracts), Nov 2012; 120: 583
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Bortezomib
mesh term: Lenograstim
sharing ipd: No