<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/NCT01735604</url>
  </required_header>
  <id_info>
    <org_study_id>CHN-PLAGH-BT-001</org_study_id>
    <nct_id>NCT01735604</nct_id>
  </id_info>
  <brief_title>Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy</brief_title>
  <official_title>Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese PLA General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      RATIONALE: Placing a gene that has been created in the laboratory into white blood cells may&#xD;
      make the body build an immune response to kill cancer cells.&#xD;
&#xD;
      PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in&#xD;
      treating patients with B-cell leukemia or lymphoma that is resistant or refractory to&#xD;
      chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced&#xD;
      with the anti-CD20 vector (referred to as CART-20 cells).&#xD;
&#xD;
      II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood&#xD;
      will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB over time.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. For patients with detectable disease, measure anti-tumor response due to CART-20 cell&#xD;
      infusions.&#xD;
&#xD;
      II. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.&#xD;
&#xD;
      III. For patients with stored or accessible tumor cells (such as patients with active CLL,&#xD;
      ALL, etc) determine tumor cell killing by CART-20 cells in vitro.&#xD;
&#xD;
      IV. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and&#xD;
      assess correlation with loss of detectable CART-20 (loss of engraftment).&#xD;
&#xD;
      V. Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).&#xD;
&#xD;
      OUTLINE: Patients are assigned groups according to order of enrollment.&#xD;
&#xD;
      Patients receive anti-CD20-CAR lentivirus vector-transduced autologous T cells with&#xD;
      41BB-gamma vector for 3-5 days in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed intensively for 6 months, every 3&#xD;
      months for 2 years, and annually thereafter for 13 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2013</start_date>
  <completion_date type="Anticipated">October 2018</completion_date>
  <primary_completion_date type="Anticipated">May 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Occurrence of study related adverse events</measure>
    <time_frame>Until week 24</time_frame>
    <description>defined as &gt;= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor responses to CART-20 cell infusions</measure>
    <time_frame>Baseline and post-infusion</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Hematopoietic/Lymphoid Cancer</condition>
  <condition>Adult Acute Lymphoblastic Leukemia in Remission</condition>
  <condition>B-cell Adult Acute Lymphoblastic Leukemia</condition>
  <condition>B-cell Chronic Lymphocytic Leukemia</condition>
  <condition>Prolymphocytic Leukemia</condition>
  <condition>Recurrent Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Recurrent Grade 1 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 2 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 3 Follicular Lymphoma</condition>
  <condition>Recurrent Mantle Cell Lymphoma</condition>
  <condition>Refractory Chronic Lymphocytic Leukemia</condition>
  <condition>Stage III Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Stage III Chronic Lymphocytic Leukemia</condition>
  <condition>Stage III Grade 1 Follicular Lymphoma</condition>
  <condition>Stage III Grade 2 Follicular Lymphoma</condition>
  <condition>Stage III Grade 3 Follicular Lymphoma</condition>
  <condition>Stage III Mantle Cell Lymphoma</condition>
  <condition>Stage IV Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Stage IV Chronic Lymphocytic Leukemia</condition>
  <condition>Stage IV Grade 1 Follicular Lymphoma</condition>
  <condition>Stage IV Grade 2 Follicular Lymphoma</condition>
  <condition>Stage IV Grade 3 Follicular Lymphoma</condition>
  <condition>Stage IV Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>anti-CD20-CAR T cell</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1 Patients receive anti-CD20-CAR lentiviral vector-transduced autologous T cells with 41BB vector for 3-5 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>anti-CD20-CAR vector-transduced autologous T cells</intervention_name>
    <description>anti-CD20-CAR vector-transduced autologous T cells</description>
    <arm_group_label>anti-CD20-CAR T cell</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>genetically engineered lymphocyte therapy</intervention_name>
    <description>genetically engineered lymphocyte therapy</description>
    <arm_group_label>anti-CD20-CAR T cell</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  •Male and female subjects with CD20+ B cell malignancies in patients with no available&#xD;
             curative treatment options (such as autologous or allogeneic SCT) who have limited&#xD;
             prognosis (several months to &lt; 2 year survival) with currently available therapies&#xD;
             will be enrolled&#xD;
&#xD;
               -  CD20+ leukemia or lymphoma&#xD;
&#xD;
               -  ALL in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid&#xD;
                  disease, or lack of available family member or unrelated donor&#xD;
&#xD;
               -  Follicular lymphoma, previously identified as CD20+:&#xD;
&#xD;
               -  At least 2 prior combination chemotherapy regimens (not including single agent&#xD;
                  monoclonal antibody (Rituxan) therapy&#xD;
&#xD;
               -  Stage III-IV disease&#xD;
&#xD;
               -  Less than 1 year between last chemotherapy and progression (i.e. most recent&#xD;
                  progression free interval &lt; 1 year)&#xD;
&#xD;
               -  Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)&#xD;
&#xD;
               -  CLL:&#xD;
&#xD;
               -  At least 2 prior chemotherapy regimens (not including single agent monoclonal&#xD;
                  antibody (Rituxan) therapy. Patients with high risk disease manifested by&#xD;
                  deletion chromosome 17p will be eligible if they fail to achieve a CR to initial&#xD;
                  therapy or progress within 2 years of 1 prior&#xD;
&#xD;
               -  Less than 2 years between last chemotherapy and progression (i.e. most recent&#xD;
                  progression free interval &lt; 2 years)&#xD;
&#xD;
               -  Not eligible or appropriate for conventional allogeneic SCT&#xD;
&#xD;
               -  Patients who achieve only a partial response to FCR as initial therapy will be&#xD;
                  eligible.&#xD;
&#xD;
               -  Mantle cell lymphoma:&#xD;
&#xD;
               -  Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate&#xD;
                  for conventional allogeneic or autologous SCT&#xD;
&#xD;
               -  Disease responding or stable after most recent therapy (chemotherapy, MoAb,&#xD;
                  etc...)&#xD;
&#xD;
               -  Relapsed after prior autologous SCT&#xD;
&#xD;
               -  B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at&#xD;
                  least 1 prior therapy and not eligible for allogeneic SCT&#xD;
&#xD;
               -  Diffuse large cell lymphoma, previously identified as CD20+:&#xD;
&#xD;
               -  Residual disease after primary therapy and not eligible for autologous SCT&#xD;
&#xD;
               -  Relapsed after prior autologous SCT&#xD;
&#xD;
               -  Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate&#xD;
                  of conventional allogeneic or autologous SCT&#xD;
&#xD;
               -  Expected survival &gt; 12 weeks&#xD;
&#xD;
               -  Creatinine &lt; 2.5 mg/dl&#xD;
&#xD;
               -  ALT/AST &lt; 3x normal&#xD;
&#xD;
               -  Bilirubin &lt; 2.0 mg/dl&#xD;
&#xD;
               -  Any relapse after prior autologous SCT will make patient eligible regardless of&#xD;
                  other prior therapy&#xD;
&#xD;
               -  Adequate venous access for apheresis, and no other contraindications for&#xD;
                  leukapheresis&#xD;
&#xD;
               -  Voluntary informed consent is given&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  •Pregnant or lactating women&#xD;
&#xD;
               -  The safety of this therapy on unborn children is not known&#xD;
&#xD;
               -  Female study participants of reproductive potential must have a negative serum or&#xD;
                  urine pregnancy test performed within 48 hours before infusion&#xD;
&#xD;
               -  Uncontrolled active infection&#xD;
&#xD;
               -  Active hepatitis B or hepatitis C infection&#xD;
&#xD;
               -  Concurrent use of systemic steroids. Recent or current use of inhaled steroids is&#xD;
                  not exclusionary&#xD;
&#xD;
               -  Previously treatment with any gene therapy products&#xD;
&#xD;
               -  Feasibility assessment during screening demonstrates &lt; 30% transduction of target&#xD;
                  lymphocytes, or insufficient expansion (&lt; 5-fold) in response to CD3/CD28&#xD;
                  costimulation&#xD;
&#xD;
               -  Any uncontrolled active medical disorder that would preclude participation as&#xD;
                  outlined&#xD;
&#xD;
               -  HIV infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Han weidong, doctor</last_name>
    <phone>+86-10-66937463</phone>
    <email>hanwdrsw@sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bo jian, doctor</last_name>
    <phone>+86-10-13801257802</phone>
    <email>boj301@sina.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Biotherapeutic Department of Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Han weidong, Doctor</last_name>
      <phone>+86-10-66937463</phone>
      <email>hanwdrsw@sina.com</email>
    </contact>
    <contact_backup>
      <last_name>Bo jian, Doctor</last_name>
      <phone>86-10-13801257802</phone>
      <email>boj301@sina.com</email>
    </contact_backup>
    <investigator>
      <last_name>Han weidong, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bo Jian, Doctor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wang Yao, Master</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>November 23, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>September 27, 2015</last_update_submitted>
  <last_update_submitted_qc>September 27, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 29, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Han weidong</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Leukemia, Prolymphocytic</mesh_term>
    <mesh_term>Recurrence</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/NCT01735604
org study id: CHN-PLAGH-BT-001
nct id: NCT01735604
lead sponsor: 
has dmc: Yes
RATIONALE: Placing a gene that has been created in the laboratory into white blood cells may
      make the body build an immune response to kill cancer cells.

      PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in
      treating patients with B-cell leukemia or lymphoma that is resistant or refractory to
      chemotherapy.
PRIMARY OBJECTIVES:

      I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced
      with the anti-CD20 vector (referred to as CART-20 cells).

      II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood
      will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB over time.

      SECONDARY OBJECTIVES:

      I. For patients with detectable disease, measure anti-tumor response due to CART-20 cell
      infusions.

      II. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.

      III. For patients with stored or accessible tumor cells (such as patients with active CLL,
      ALL, etc) determine tumor cell killing by CART-20 cells in vitro.

      IV. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and
      assess correlation with loss of detectable CART-20 (loss of engraftment).

      V. Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).

      OUTLINE: Patients are assigned groups according to order of enrollment.

      Patients receive anti-CD20-CAR lentivirus vector-transduced autologous T cells with
      41BB-gamma vector for 3-5 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed intensively for 6 months, every 3
      months for 2 years, and annually thereafter for 13 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of study related adverse events
time frame: Until week 24
description: defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
measure: Anti-tumor responses to CART-20 cell infusions
time frame: Baseline and post-infusion
arm group label: anti-CD20-CAR T cell
arm group type: Experimental
description: Arm 1 Patients receive anti-CD20-CAR lentiviral vector-transduced autologous T cells with 41BB vector for 3-5 days in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: anti-CD20-CAR vector-transduced autologous T cells
description: anti-CD20-CAR vector-transduced autologous T cells
arm group label: anti-CD20-CAR T cell
intervention type: Other
intervention name: genetically engineered lymphocyte therapy
description: genetically engineered lymphocyte therapy
arm group label: anti-CD20-CAR T cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Han weidong, doctor
phone: +86-10-66937463
email: hanwdrsw@sina.com
last name: Bo jian, doctor
phone: +86-10-13801257802
email: boj301@sina.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Han weidong
investigator title: PI
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, Follicular
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Leukemia, Prolymphocytic
mesh term: Recurrence