<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/NCT03274219</url>
  </required_header>
  <id_info>
    <org_study_id>CRB-402</org_study_id>
    <nct_id>NCT03274219</nct_id>
  </id_info>
  <brief_title>Study of bb21217 in Multiple Myeloma</brief_title>
  <official_title>A Phase 1 Study of bb21217, an Anti-BCMA CAR T Cell Drug Product, in Relapsed and/or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>bluebird bio</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>bluebird bio</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study CRB-402 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb21217 in&#xD;
      adults with relapsed/refractory multiple myeloma (MM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part A of the study will be Dose Escalation followed by Part B, an expansion cohort.&#xD;
&#xD;
      Following consent, enrolled subjects will undergo a leukapheresis procedure to collect&#xD;
      autologous mononuclear cells for manufacture of investigational drug product (bb21217).&#xD;
      Following manufacture of the drug product, subjects will receive lymphodepletion prior to&#xD;
      bb21217 infusion. All subjects will then be followed for up to 60 months in Study CRB-402.&#xD;
&#xD;
      All subjects who complete the study, as well as those who withdraw from the study after&#xD;
      receiving bb21217 for reasons other than death or meeting the early termination criteria,&#xD;
      will be asked to continue to undergo long-term follow-up in a companion study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 16, 2017</start_date>
  <completion_date type="Anticipated">October 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2025</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>Incidence of adverse events (AEs), DLTs, and changes in laboratory results</measure>
    <time_frame>Day 1 through Month 60</time_frame>
    <description>Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-specific response criteria</measure>
    <time_frame>Month 1 through Month 60</time_frame>
    <description>• Disease-specific response criteria including, but not limited to: complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>bb21217 Experimental Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bb21217</intervention_name>
    <description>autologous T cells transduced ex-vivo with anti-BCMA CAR lentiviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA, suspended in cryopreservative solution</description>
    <arm_group_label>bb21217 Experimental Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥18 years of age at the time of signing informed consent&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  Diagnosis of MM with relapsed or refractory disease and have had at least 3 different&#xD;
             prior lines of therapy with previous exposure to PI, IMiDs, and a CD38 antibody. Have&#xD;
             undergone at least 2 consecutive cycles of treatment for each therapy, unless PD was&#xD;
             the best response to the therapy. Refractory to their last line of therapy.&#xD;
&#xD;
          -  Subjects must have measurable disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with known central nervous system disease&#xD;
&#xD;
          -  Inadequate hepatic function&#xD;
&#xD;
          -  Inadequate renal function&#xD;
&#xD;
          -  Inadequate bone marrow function&#xD;
&#xD;
          -  Presence of active infection within 72 hours&#xD;
&#xD;
          -  Subjects with a history of stroke, unstable angina, myocardial infarction, or&#xD;
             ventricular arrhythmia requiring medication or mechanical control&#xD;
&#xD;
          -  Significant co-morbid condition or disease which in the judgment of the Investigator&#xD;
             would place the subject at undue risk or interfere with the study; examples include,&#xD;
             but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic&#xD;
             injury, and other conditions&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) positivity&#xD;
&#xD;
          -  Known hepatitis A virus (HAV), hepatitis B virus (HBV) or hepatitis C virus (HCV)&#xD;
             positivity with evidence of ongoing infection.&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Previous history of an allogeneic bone marrow transplantation, treatment with any gene&#xD;
             therapy based therapeutic for cancer, or BCMA-targeted therapy&#xD;
&#xD;
          -  Inadequate pulmonary function defined as oxygen saturation (SaO2) &lt;92% on room air&#xD;
&#xD;
          -  Subjects who have a history of plasma cell leukemia, active plasma cell leukemia,&#xD;
             Waldenstrom's macroglobulinemia, POEMS, or clinically significant 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>Anna Truppel-Hartmann, MD</last_name>
    <role>Study Director</role>
    <affiliation>bluebird bio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSF Medical Center at Parnassus</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Insitute, Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Cancer Center</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Theurer Cancer Center at Hackensack UMC</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>March 17, 2021</last_update_submitted>
  <last_update_submitted_qc>March 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2021</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>
  <!-- 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/NCT03274219
org study id: CRB-402
nct id: NCT03274219
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Study CRB-402 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb21217 in
      adults with relapsed/refractory multiple myeloma (MM).
Part A of the study will be Dose Escalation followed by Part B, an expansion cohort.

      Following consent, enrolled subjects will undergo a leukapheresis procedure to collect
      autologous mononuclear cells for manufacture of investigational drug product (bb21217).
      Following manufacture of the drug product, subjects will receive lymphodepletion prior to
      bb21217 infusion. All subjects will then be followed for up to 60 months in Study CRB-402.

      All subjects who complete the study, as well as those who withdraw from the study after
      receiving bb21217 for reasons other than death or meeting the early termination criteria,
      will be asked to continue to undergo long-term follow-up in a companion study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events (AEs), DLTs, and changes in laboratory results
time frame: Day 1 through Month 60
description: Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs)
measure: Disease-specific response criteria
time frame: Month 1 through Month 60
description: • Disease-specific response criteria including, but not limited to: complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma
arm group label: bb21217 Experimental Arm
arm group type: Experimental
intervention type: Biological
intervention name: bb21217
description: autologous T cells transduced ex-vivo with anti-BCMA CAR lentiviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA, suspended in cryopreservative solution
arm group label: bb21217 Experimental Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anna Truppel-Hartmann, MD
role: Study Director
affiliation: bluebird bio
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell