<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/NCT02193191</url>
  </required_header>
  <id_info>
    <org_study_id>13-229</org_study_id>
    <nct_id>NCT02193191</nct_id>
  </id_info>
  <brief_title>Escalation of Plerixafor for Mobilization of CD34+ Hematopoietic Progenitor Cells and Evaluation of Globin Gene Transfer in Patients With Sickle Cell Disease</brief_title>
  <official_title>Safety and Efficacy Trial of Escalation of Plerixafor for Mobilization of CD34+ Hematopoietic Progenitor Cells and Evaluation of Globin Gene Transfer in Patients With Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>New York Blood Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <brief_summary>
    <textblock>
      The purpose of this research study is to test the safety and efficacy of a drug called&#xD;
      Plerixafor. Plerixafor is approved by the US FDA for use in increasing blood stem cell counts&#xD;
      before collection in cancer patients. It is not yet approved for patients with sickle cell&#xD;
      disease. The investigators want to find out if Plerixafor can be used to increase cell counts&#xD;
      in patients with sickle cell disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Anticipated">July 2025</completion_date>
  <primary_completion_date type="Anticipated">July 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>safety</measure>
    <time_frame>up to 30 days</time_frame>
    <description>Safety is assessed using a dose limiting toxicity (DLT) endpoint. Definition of a DLT is the occurrence of any of the below events that meets the following criteria: The occurrence of a vasoocclusive crisis requiring hospitalization, acute chest syndrome, CNS acute event, or any other disease related ischemic-based adverse event (AE) should be considered as a DLT, if occurring in the 48 hours DLT observation period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>efficacy</measure>
    <time_frame>≥ 30/ul at either 6-12 hours or 24-48 hours post plerixafor.</time_frame>
    <description>Efficacy is defined as 100% of evaluable patients reaching a PB CD34 concentration ≥ 30/uL.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Plerixafor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a single dose of subcutaneous plerixafor with peripheral blood studies at approximately 0-2 hours before, approximately 6-12 hours after, and approximately 20-48 hours after plerixafor administration, with leukapheresis in the last 3 patients on the protocol. Collected HPCs will be transferred to the MSKCC CTCEF to determine if the HPCs are amenable to transduction with a lentiviral vector encoding the normal ß- globin gene.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Plerixafor</intervention_name>
    <arm_group_label>Plerixafor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have confirmed and measurable Sickle Cell Disease, defined by SS or Sβ&#xD;
             thalassemia confirmed by hemoglobin fractionation.&#xD;
&#xD;
          -  ≥ 18 to 65 years of age&#xD;
&#xD;
          -  Patient must have a ECOG performance status ≤2 or Karnofsky score &gt; 70%&#xD;
&#xD;
          -  Patients must have acceptable organ and marrow function as defined below:&#xD;
&#xD;
               -  WBC ≥ 3,000/μL&#xD;
&#xD;
               -  ANC ≥ 1,500/μL&#xD;
&#xD;
               -  platelets ≥150,000//μL&#xD;
&#xD;
               -  Hemoglobin ≥ 6 gm/dL&#xD;
&#xD;
               -  Calculated creatinine clearance ≥ 60ml/min * *Using the Cockcroft-gault equation&#xD;
                  [140 - Age(yrs)] [Weight(kg)] x 0.85 if Female 72 [Serum Creatinine (mg/dL]&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while participating in this study, she should inform her treating physician&#xD;
             immediately.&#xD;
&#xD;
          -  Each patient must be willing to participate as a research subject and must sign an&#xD;
             informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are:&#xD;
&#xD;
               -  Receiving or received treatment with an investigational agent within 4 weeks&#xD;
                  prior to entering the study OR&#xD;
&#xD;
               -  have not recovered from adverse events due to agents administered more than 4&#xD;
                  weeks earlier as determined by the treating physician.&#xD;
&#xD;
          -  Patients with ALT(SGPT) &gt; 2.5 X upper limit of normal&#xD;
&#xD;
          -  Patients with a creatinine clearance of &lt; 60 ml/min&#xD;
&#xD;
          -  Patients who have uncontrolled illness including, but not limited to:&#xD;
&#xD;
               -  Ongoing or active infection&#xD;
&#xD;
               -  Emergency room admission or hospitalization in the past 14 days&#xD;
&#xD;
               -  Major surgery in the past 30 days&#xD;
&#xD;
               -  Medical/psychiatric illness/social situations that would limit compliance with&#xD;
                  study requirements as determined by the treating physician.&#xD;
&#xD;
          -  Female patients who are pregnant or breast-feeding&#xD;
&#xD;
          -  Patients with active hepatitis B, hepatitis C, or HIV infection&#xD;
&#xD;
          -  Patients with poor cardiac function as defined by an ejection fraction &lt; 40% are&#xD;
             excluded due to potential poor tolerance of the fluid shifts with leukapheresis (only&#xD;
             for patients enrolled on second phase of protocol for Leukapheresis).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roni Tamari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Roni Tamari, MD</last_name>
    <phone>646-608-3738</phone>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Michel Sadelain, MD, PhD</last_name>
    <phone>212-639-6190</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roni Tamari, MD</last_name>
      <phone>646-608-3738</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>August 8, 2023</last_update_submitted>
  <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Plerixafor</keyword>
  <keyword>13-229</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Plerixafor</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/NCT02193191
org study id: 13-229
nct id: NCT02193191
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
The purpose of this research study is to test the safety and efficacy of a drug called
      Plerixafor. Plerixafor is approved by the US FDA for use in increasing blood stem cell counts
      before collection in cancer patients. It is not yet approved for patients with sickle cell
      disease. The investigators want to find out if Plerixafor can be used to increase cell counts
      in patients with sickle cell disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: safety
time frame: up to 30 days
description: Safety is assessed using a dose limiting toxicity (DLT) endpoint. Definition of a DLT is the occurrence of any of the below events that meets the following criteria: The occurrence of a vasoocclusive crisis requiring hospitalization, acute chest syndrome, CNS acute event, or any other disease related ischemic-based adverse event (AE) should be considered as a DLT, if occurring in the 48 hours DLT observation period.
measure: efficacy
time frame: ≥ 30/ul at either 6-12 hours or 24-48 hours post plerixafor.
description: Efficacy is defined as 100% of evaluable patients reaching a PB CD34 concentration ≥ 30/uL.
arm group label: Plerixafor
arm group type: Experimental
description: Patients will receive a single dose of subcutaneous plerixafor with peripheral blood studies at approximately 0-2 hours before, approximately 6-12 hours after, and approximately 20-48 hours after plerixafor administration, with leukapheresis in the last 3 patients on the protocol. Collected HPCs will be transferred to the MSKCC CTCEF to determine if the HPCs are amenable to transduction with a lentiviral vector encoding the normal ß- globin gene.
intervention type: Drug
intervention name: Plerixafor
arm group label: Plerixafor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Roni Tamari, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Roni Tamari, MD
phone: 646-608-3738
last name: Michel Sadelain, MD, PhD
phone: 212-639-6190
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Plerixafor