<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/NCT01683279</url>
  </required_header>
  <id_info>
    <org_study_id>PLAT-01</org_study_id>
    <nct_id>NCT01683279</nct_id>
  </id_info>
  <brief_title>A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia</brief_title>
  <official_title>Pediatric Leukemia Adoptive Therapy (PLAT)-01: A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Relapsed Pediatric CD19+ Acute Lymphoblastic Leukemia Using Autologous T-cells Lentivirally Transduced To Express a CD19-Specific Chimeric Antigen Receptor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seattle Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seattle Children's Hospital</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with relapsed leukemia often develop resistance to chemotherapy. For this reason, we&#xD;
      are attempting to use a patient's own T cells, which can be genetically modified to expresses&#xD;
      a chimeric antigen receptor(CAR). The CAR enables the T cell to recognize and kill the&#xD;
      leukemic cells though the recognition of CD19, a protein expressed on the surface of the&#xD;
      majority of pediatric ALL. This is a phase I study designed to determine the maximum&#xD;
      tolerated dose of the CAR+ T cells and define the toxicity of the treatment. As a secondary&#xD;
      aim, we will be looking at the efficacy of the T cells on eradicating the patient's leukemic&#xD;
      cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Upon meeting the eligibility requirements and enrolling on study, subjects will undergo a&#xD;
      blood draw to obtain the T cells for the generation of the CD19 CAR+ T cells. The T cells are&#xD;
      isolated from the blood, transduced with a lentivirus to express the CD19 CAR, and expanded&#xD;
      in culture over a three week period. During the process of cell generation, subjects will&#xD;
      continue to be cared for by their primary oncologist and may undergo additional treatment&#xD;
      directed at the leukemia during this time.&#xD;
&#xD;
      After the CAR+ T cells have been generated, the subject undergoes a disease assessment and&#xD;
      will be admitted to the hospital to receive 2 days of cyclophosphamide for lymphodepletion&#xD;
      and reduction of disease burden. Several days later, the subject will receive an infusion of&#xD;
      the CAR+ T cells.&#xD;
&#xD;
      Following treatment with the CAR+ T cells, subjects will be intensely followed for 6 weeks&#xD;
      with serial blood testing and re-evaluation of disease status with bone marrow aspirates.&#xD;
      After 6 weeks, the subjects clinical care will be resumed by their primary oncologist, and it&#xD;
      is possible that they would receive additionally chemotherapy or a stem cell transplant.&#xD;
&#xD;
      Upon completion of the study, subjects will be followed at least annually with a either a&#xD;
      medical history, physical exam and blood tests or a phone call/questionnaire for 15 years.&#xD;
      This follow up will help to determine if the subject develops any long-term health problems&#xD;
      related to the CAR+ T cells including a new cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 25, 2012</start_date>
  <completion_date type="Anticipated">January 7, 2030</completion_date>
  <primary_completion_date type="Actual">January 7, 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>Number of Participant with Adverse Events</measure>
    <time_frame>42 days</time_frame>
    <description>The safety of the T cell infusion will be described and the maximum tolerated dose determined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Persistence of the CD19 CAR+ T cells</measure>
    <time_frame>42 days</time_frame>
    <description>Patients will be followed for 42 days to determine if the transferred T cells remain detectable in the blood and bone marrow</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine if there is anti-leukemic activity of the CD19 CAR+ T cells</measure>
    <time_frame>42 days</time_frame>
    <description>Patients will have their bone marrow assessed following the T cell infusion to determine if their disease responded to the treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>B Cell Leukemia</condition>
  <arm_group>
    <arm_group_label>CAR+ T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive two days of cyclophosphamide for a total of 3g/m^2 followed several days later by a single dose of Autologous CD19 CAR+ EGFTt + T cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous CD19 CAR+ EGFTt + T cells</intervention_name>
    <description>Autologous T cell modified to express a CD19 specific CAR and a truncated EGFRt tag</description>
    <arm_group_label>CAR+ T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CD19+ Leukemia in 1st marrow relapse with MRD at the end of 1st month of re-induction&#xD;
&#xD;
          -  CD19+ Leukemia in 2nd or greater relapse&#xD;
&#xD;
          -  CD19+ Leukemia with indication for HCT, but has contraindication&#xD;
&#xD;
          -  Age between 1 and 26 years of age&#xD;
&#xD;
          -  Karnofsky of &gt;50 or Lansky &gt;50&#xD;
&#xD;
          -  Life Expectancy &gt;12 weeks&#xD;
&#xD;
          -  Able to tolerate a blood draw of 4-6mL/kg&#xD;
&#xD;
          -  Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or&#xD;
             radiotherapy&#xD;
&#xD;
          -  absolute lymphocyte count of &gt;/=750 cell/mm3 or &gt;/=500 is &gt;20kg&#xD;
&#xD;
          -  creatinine clearance or radioisotope GFR &gt;/= 70mL/min/1.73m2 OR normal serum&#xD;
             creatinine based on age/gender&#xD;
&#xD;
          -  total bilirubin &lt;/= 1.5x upper limit normal OR direct bilirubin &lt;/= 1.5mg/dl&#xD;
&#xD;
          -  ALT &lt;/= 3x upper limit normal&#xD;
&#xD;
          -  corrected QTc &lt;450msec of ECG&#xD;
&#xD;
          -  Shortening Fraction &gt;28% by ECHO or Ejection Fraction &gt;50% by MUGA&#xD;
&#xD;
          -  Documented negative HIV, Hep B and Hep C&#xD;
&#xD;
          -  Agree to long-term follow up for up to 15 years if they receive T cell infusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Philadelphia Positive Leukemia&#xD;
&#xD;
          -  Prior Allogeneic Stem Cell Transplant&#xD;
&#xD;
          -  CNS 2 or 3&#xD;
&#xD;
          -  prior cellular immunotherapy with chimeric antigen receptor modified T cells&#xD;
&#xD;
          -  fully humanized antibodies within three half lives&#xD;
&#xD;
          -  systemic corticosteroids within 7 days of enrollment&#xD;
&#xD;
          -  requires supplemental oxygen or has a chest X-ray with an infectious process&#xD;
&#xD;
          -  CNS pathology (seizure disorder, paresis, aphasia, cerebrovascular&#xD;
             ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic&#xD;
             brain syndrome, psychosis, coordination or movement disorder)&#xD;
&#xD;
          -  Pregnant or breastfeeding women. Female participant of reproductive age must have a&#xD;
             negative pregnancy test and agree to contraception for 1 year after T cell infusion.&#xD;
&#xD;
          -  Active Malignancy other than CD19+ Leukemia&#xD;
&#xD;
          -  Active severe infection defined as a positive blood culture within 48 hours of study&#xD;
             enrollment or a fever &gt;38.2C AND clinical signs of infection within 48 hours of study&#xD;
             enrollment&#xD;
&#xD;
          -  Patient has a concurrent medical condition, that in the opinion of the protocol PI or&#xD;
             designee, would prevent the patient from undergoing protocol-based therapy.&#xD;
&#xD;
          -  Trisomy 21&#xD;
&#xD;
          -  Primary immunodeficiency/bone marrow failure syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>26 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebecca Gardner, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Seattle Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>June 27, 2023</last_update_submitted>
  <last_update_submitted_qc>June 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seattle Children's Hospital</investigator_affiliation>
    <investigator_full_name>Colleen Annesley</investigator_full_name>
    <investigator_title>Medical Director, Seattle Children's Therapeutics</investigator_title>
  </responsible_party>
  <keyword>pediatric</keyword>
  <keyword>acute lymphoblastic leukemia</keyword>
  <keyword>CD19</keyword>
  <keyword>Chimeric Antigen Receptor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-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/NCT01683279
org study id: PLAT-01
nct id: NCT01683279
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Patients with relapsed leukemia often develop resistance to chemotherapy. For this reason, we
      are attempting to use a patient's own T cells, which can be genetically modified to expresses
      a chimeric antigen receptor(CAR). The CAR enables the T cell to recognize and kill the
      leukemic cells though the recognition of CD19, a protein expressed on the surface of the
      majority of pediatric ALL. This is a phase I study designed to determine the maximum
      tolerated dose of the CAR+ T cells and define the toxicity of the treatment. As a secondary
      aim, we will be looking at the efficacy of the T cells on eradicating the patient's leukemic
      cells.
Upon meeting the eligibility requirements and enrolling on study, subjects will undergo a
      blood draw to obtain the T cells for the generation of the CD19 CAR+ T cells. The T cells are
      isolated from the blood, transduced with a lentivirus to express the CD19 CAR, and expanded
      in culture over a three week period. During the process of cell generation, subjects will
      continue to be cared for by their primary oncologist and may undergo additional treatment
      directed at the leukemia during this time.

      After the CAR+ T cells have been generated, the subject undergoes a disease assessment and
      will be admitted to the hospital to receive 2 days of cyclophosphamide for lymphodepletion
      and reduction of disease burden. Several days later, the subject will receive an infusion of
      the CAR+ T cells.

      Following treatment with the CAR+ T cells, subjects will be intensely followed for 6 weeks
      with serial blood testing and re-evaluation of disease status with bone marrow aspirates.
      After 6 weeks, the subjects clinical care will be resumed by their primary oncologist, and it
      is possible that they would receive additionally chemotherapy or a stem cell transplant.

      Upon completion of the study, subjects will be followed at least annually with a either a
      medical history, physical exam and blood tests or a phone call/questionnaire for 15 years.
      This follow up will help to determine if the subject develops any long-term health problems
      related to the CAR+ T cells including a new cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participant with Adverse Events
time frame: 42 days
description: The safety of the T cell infusion will be described and the maximum tolerated dose determined.
measure: Persistence of the CD19 CAR+ T cells
time frame: 42 days
description: Patients will be followed for 42 days to determine if the transferred T cells remain detectable in the blood and bone marrow
measure: Determine if there is anti-leukemic activity of the CD19 CAR+ T cells
time frame: 42 days
description: Patients will have their bone marrow assessed following the T cell infusion to determine if their disease responded to the treatment
arm group label: CAR+ T cells
arm group type: Experimental
description: Subjects will receive two days of cyclophosphamide for a total of 3g/m^2 followed several days later by a single dose of Autologous CD19 CAR+ EGFTt + T cells
intervention type: Biological
intervention name: Autologous CD19 CAR+ EGFTt + T cells
description: Autologous T cell modified to express a CD19 specific CAR and a truncated EGFRt tag
arm group label: CAR+ T cells
criteria: 
gender: All
minimum age: 1 Year
maximum age: 26 Years
healthy volunteers: No
last name: Rebecca Gardner, MD
role: Study Chair
affiliation: Seattle Children's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Seattle Children's Hospital
investigator full name: Colleen Annesley
investigator title: Medical Director, Seattle Children's Therapeutics
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell