<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/NCT03798509</url>
  </required_header>
  <id_info>
    <org_study_id>HRAIN01-ALL01</org_study_id>
    <nct_id>NCT03798509</nct_id>
  </id_info>
  <brief_title>Human CD19 Targeted T Cells Injection Therapy for Relapsed and Refractory CD19-positive Leukemia</brief_title>
  <official_title>A Phase I Clinical Trial to Evaluate the Safety and Tolerability of Human CD19 Targeted T Cells Injection for Subjects With Relapsed and Refractory CD19-positive B-cell Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hrain Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hrain Biotechnology Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety and tolerance of human CD19 targeted T Cells injection for the&#xD;
      treatment of relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia.&#xD;
      Patients will be given a conditioning chemotherapy regimen of fludarabine and&#xD;
      cyclophosphamide followed by a single infusion of CD19 CAR+ T cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia can&#xD;
      participate if all eligibility criteria are met. Tests required to determine eligibility&#xD;
      include disease assessments, a physical exam, electrocardiograph and blood draws.&#xD;
      Participants receive chemotherapy prior to the infusion of CD19 CAR+ T cells. After the&#xD;
      infusion, participants will be followed for side effects and effect of CD19 CAR+ T cells.&#xD;
      Study procedures may be performed while hospitalized.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2022</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>DLT</measure>
    <time_frame>28 days post infusion</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of CAR-positive T cells in circulation</measure>
    <time_frame>2 years post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The concentration of CD19-positive B cells in peripheral blood.</measure>
    <time_frame>2 years post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR) after administration</measure>
    <time_frame>90 days post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of remission (DOR) after administration</measure>
    <time_frame>2 years post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progress Free Survival (PFS) after administration</measure>
    <time_frame>2 years post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)after administration</measure>
    <time_frame>2 years post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The immunogenicity of Human CD19 targeted T Cells Injection. (the detection of human anti-mouse antibody)</measure>
    <time_frame>2 years post infusion</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>CD19-positive</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>Human CD19 targeted T Cells Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Human CD19 targeted T Cells Injection</intervention_name>
    <description>Autologous genetically modified anti-CD19 CAR transduced T cells</description>
    <arm_group_label>Human CD19 targeted T Cells Injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18 to 70 Years Old, Male and female;&#xD;
&#xD;
          2. Expected survival &gt; 12 weeks;&#xD;
&#xD;
          3. ECOG score 0-1;&#xD;
&#xD;
          4. Bone marrow examination clearly diagnosed as CD19 positive B-cell acute lymphoblastic&#xD;
             leukemia and who met one of the following conditions:&#xD;
&#xD;
               1. Those who failed to achieve CR after at least 2 courses of standard chemotherapy&#xD;
                  or had early relapse after complete remission (&lt;12 months) or late relapse after&#xD;
                  complete remission (≥ 12 months) and failed to achieve CR after 1 course of&#xD;
                  standard chemotherapy;&#xD;
&#xD;
               2. For Ph+ ALL: in addition to receiving at least 2 courses of standard&#xD;
                  chemotherapy, at least two TKIs should be treated with no complete remission or&#xD;
                  relapse after complete remission (Patients who cannot tolerate TKI therapy or&#xD;
                  have TKI treatment contraindications or have T315i mutation are excluded);&#xD;
&#xD;
               3. Those who relapse after stem cell transplantation are not affected by previous&#xD;
                  treatments;&#xD;
&#xD;
          5. The venous access required for collection can be established and mononuclear cell&#xD;
             collection can be determined by the investigators;&#xD;
&#xD;
          6. Liver, kidney and cardiopulmonary functions meet the following requirements:&#xD;
&#xD;
               1. Creatinine is in the normal range;&#xD;
&#xD;
               2. Left ventricular ejection fraction &gt;50%;&#xD;
&#xD;
               3. Baseline oxygen saturation&gt;92%;&#xD;
&#xD;
               4. Total bilirubin ≤ 2×ULN; ALT and AST ≤2.5 × ULN;&#xD;
&#xD;
          7. Able to understand and sign the Informed Consent Document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Graft-versus-host disease (GVHD), or need to use immunosuppressants;&#xD;
&#xD;
          2. Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to&#xD;
             screening, in addition to adequately treated cervical carcinoma in situ, basal cell or&#xD;
             squamous cell skin cancer, localized prostate cancer after radical resection, and&#xD;
             ductal carcinoma in situ after radical resection;&#xD;
&#xD;
          3. Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1&#xD;
             × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive;&#xD;
             HIV antibody positive; CMV DNA positive; syphilis positive;&#xD;
&#xD;
          4. Any instability of systemic disease, including but not limited to unstable angina,&#xD;
             cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to&#xD;
             screening), myocardial infarction (within 6 months prior to screening), congestive&#xD;
             heart failure (New York heart association (NYHA) classification ≥ III), need drug&#xD;
             therapy of severe arrhythmia, liver, kidney, or metabolic disease;&#xD;
&#xD;
          5. Active or uncontrollable infection requiring systemic therapy within 14 days prior to&#xD;
             enrollment;&#xD;
&#xD;
          6. Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1&#xD;
             year after cell transfusion, or male subject whose partner plans to have a pregnancy&#xD;
             within 1 year after cell transfusion;&#xD;
&#xD;
          7. Received CAR-T treatment or other gene therapies before enrollment;&#xD;
&#xD;
          8. Patients with symptoms of central nervous system;&#xD;
&#xD;
          9. Subjects who are receiving systemic steroid treatment and requiring long-term systemic&#xD;
             steroid treatment during the treatment as determined by the investigator before&#xD;
             screening (except inhalation or topical use); And subjects treated with systemic&#xD;
             steroids (except inhalation or topical use) within 72h prior to cell transfusion;&#xD;
&#xD;
         10. The investigators consider other conditions unsuitable for enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hongliang Fang, doctor</last_name>
    <phone>021-58552006</phone>
    <email>fanghongliang@dashengbio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xianmin Song, Professor</last_name>
      <phone>021-63240090</phone>
      <phone_ext>3173</phone_ext>
      <email>shongxm@139.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>August 29, 2021</last_update_submitted>
  <last_update_submitted_qc>August 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CD19</keyword>
  <keyword>CAR-T</keyword>
  <keyword>leukemia</keyword>
  <keyword>Relapsed /Refractory</keyword>
  <keyword>B-ALL</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>
  </condition_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/NCT03798509
org study id: HRAIN01-ALL01
nct id: NCT03798509
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To evaluate the safety and tolerance of human CD19 targeted T Cells injection for the
      treatment of relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia.
      Patients will be given a conditioning chemotherapy regimen of fludarabine and
      cyclophosphamide followed by a single infusion of CD19 CAR+ T cells.
Participants with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia can
      participate if all eligibility criteria are met. Tests required to determine eligibility
      include disease assessments, a physical exam, electrocardiograph and blood draws.
      Participants receive chemotherapy prior to the infusion of CD19 CAR+ T cells. After the
      infusion, participants will be followed for side effects and effect of CD19 CAR+ T cells.
      Study procedures may be performed while hospitalized.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLT
time frame: 28 days post infusion
measure: Duration of CAR-positive T cells in circulation
time frame: 2 years post infusion
measure: The concentration of CD19-positive B cells in peripheral blood.
time frame: 2 years post infusion
measure: Overall response rate (ORR) after administration
time frame: 90 days post infusion
measure: Duration of remission (DOR) after administration
time frame: 2 years post infusion
measure: Progress Free Survival (PFS) after administration
time frame: 2 years post infusion
measure: Overall Survival (OS)after administration
time frame: 2 years post infusion
measure: The immunogenicity of Human CD19 targeted T Cells Injection. (the detection of human anti-mouse antibody)
time frame: 2 years post infusion
arm group label: Human CD19 targeted T Cells Injection
arm group type: Experimental
intervention type: Drug
intervention name: Human CD19 targeted T Cells Injection
description: Autologous genetically modified anti-CD19 CAR transduced T cells
arm group label: Human CD19 targeted T Cells Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Hongliang Fang, doctor
phone: 021-58552006
email: fanghongliang@dashengbio.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
sharing ipd: No