<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/NCT03229876</url>
  </required_header>
  <id_info>
    <org_study_id>2018CAR-00CH1</org_study_id>
    <nct_id>NCT03229876</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Evaluation of CD19-UCART</brief_title>
  <official_title>A Safety and Efficacy Study of CD19-UCART (Allogeneic Engineered T-cells Expressing Anti-CD19 Chimeric Antigen Receptor) in Patients With Relapsed or Refractory B-cell Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioray Laboratories</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Second Xiangya Hospital of Central South University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bioray Laboratories</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this study is to evaluate the safety and efficacy of ascending doses of&#xD;
      CD19-UCART in patients with relapsed or refractory B-cell hematological malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CD19-UCART is a kind of &quot;off-the-shelf&quot; product originated from health donor's PBMC.This is a&#xD;
      open-label, dose estilation study to evaluate the safety and anti-tumor efficacy of&#xD;
      CD19-UCART in the treatment of relapsed or refractory B-cell hematological malignancies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Sponsor decision&#xD;
  </why_stopped>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicities (DLTs) occurence</measure>
    <time_frame>Baseline up to 35 days after T cell infusion</time_frame>
    <description>Adverse events assessed according to NCI-CTCAE v5.0 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>At 12 weeks, and overall</time_frame>
    <description>The total response rate after 90 days of treatment with study drug (overall response rate for ALL= CR+CRi; for NHL=CR+PR);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day 90 progression-free survival</measure>
    <time_frame>Assessed up to 3 months</time_frame>
    <description>The 90-day progression-free survival rate following drug therapy.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>UCART cell survival time</measure>
    <time_frame>up to 1 year after infusion</time_frame>
    <description>The number of UCART cells surviving in the body within 90 days after receiving the study drug;</description>
  </other_outcome>
  <other_outcome>
    <measure>Progrssion-free survival</measure>
    <time_frame>up to 2 years after infusion</time_frame>
    <description>The time from treatment with study drug to tumor progression or death.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 2 years after infusion</time_frame>
    <description>the time from treatment with study drug to death by any cause.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Acute Lymphoblastic Leukemia (ALL)</condition>
  <condition>Non Hodgkin Lymphoma (NHL)</condition>
  <arm_group>
    <arm_group_label>CD19-UCART</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will be treated with 1 injection of CD19-UCART. Three escalating dose-levels (1.0-2.0x10^6/kgBW, 2.5-5.0x10^6/kgBW, 5.5-10.0x10^6/kgBW) of CD19-UCART will be evaluated using a 3+3 design. Each CD19-UCART injection will be administered at Day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD19-UCART</intervention_name>
    <description>A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.</description>
    <arm_group_label>CD19-UCART</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Voluntarily participating in this clinical study and signing the informed consent&#xD;
             form; The estimated survival period is at least one month;&#xD;
&#xD;
          2. No other serious cardiopulmonary diseases, and normal liver and kidney functions&#xD;
             (except for subjects with tumor lesions in their liver and kidneys);&#xD;
&#xD;
          3. Failure of T cell isolation during autologous CART preparation or failure of CART&#xD;
             amplification or failure to complete apheresis or disease progression resulting in&#xD;
             patients not benefiting from autologous CAR-T cell therapy; Or: T cell percentage in&#xD;
             PBMC of peripheral blood ≤ 10%; Or the disease is not effectively controlled within&#xD;
             one month after autologous CAR-T transfusion, and the patient cannot receive CAR-T&#xD;
             transfusion again;&#xD;
&#xD;
          4. Flow cytometry within two months demonstrated positive expression of CD19 in the tumor&#xD;
             (positive rate 50%-90%; Or biopsy ≥ 50% within 6 months; Or obtaining a biopsy again);&#xD;
&#xD;
          5. Hematological indicators: 1) WBC count ≥ 1.5× 10^9/L; Absolute value of neutrophils ≥&#xD;
             0.8× 10^9/L; Lymphocyte count ≥0.1×10^9/L;2) Hemoglobin ≥ 60g/L;3) Platelet count&#xD;
             ≥20×10^9/L;&#xD;
&#xD;
          6. Biochemical indicators (except for subjects with tumor foci in liver and kidney):&#xD;
             Total bilirubin (TBIL)≤1.5 times the Upper Limits of Normal (ULN); AST and ALT≤1.5&#xD;
             *ULN; Scr and BUN)≤1.5*ULN; Biochemical indicators in subjects with liver and kidney&#xD;
             invasion should meet: Total bilirubin (TBIL)≤5 *ULN;AST and ALT≤5*ULN; Scr and BUN ≤&#xD;
             5*ULN;&#xD;
&#xD;
          7. Cardiac function: Good hemodynamic stability, and the left ventricular ejection&#xD;
             fraction (LVEF) ≥ 55%;&#xD;
&#xD;
          8. Serum viral EBV-DNA, CMV-DNA, HIV antibody and syphilis antibody, HBV, HCV virus&#xD;
             quantification were all negative;&#xD;
&#xD;
          9. ECOG activity status score: 0-2 points;&#xD;
&#xD;
         10. Female subjects must have access to effective contraceptive measures (e.g., oral&#xD;
             prescription contraceptives, injectable contraceptives, intrauterine devices, double&#xD;
             blocking, contraceptive patches, male partner sterilizations) throughout the study&#xD;
             period; Serum or urine pregnancy test results must be negative at screening and&#xD;
             throughout the study;&#xD;
&#xD;
         11. Willing to comply with the rules established in this protocol;&#xD;
&#xD;
         12. Patients with relapsed/refractory CD19-positive acute B-cell leukemia (B-ALL, with the&#xD;
             age of 1-60 years) or relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL, with&#xD;
             the age of 5-65 years).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating women;&#xD;
&#xD;
          2. The following drugs or treatments should be excluded:High-dose glucocorticoids were&#xD;
             used within 72h prior to UCAR-T infusion, except for physiological alternative&#xD;
             therapies;Allogeneic cell therapies such as donor lymphocyte transfusion within 6&#xD;
             weeks prior to UCAR-T transfusion;GVHD treatment;&#xD;
&#xD;
          3. Single extramedullary relapse B-ALL;&#xD;
&#xD;
          4. Suffering from severe mental disorder;&#xD;
&#xD;
          5. Active autoimmune diseases requiring immunotherapy;&#xD;
&#xD;
          6. History of other malignant tumors;&#xD;
&#xD;
          7. Patients with severe cardiovascular disease;&#xD;
&#xD;
          8. Organ function is in the following abnormalities;&#xD;
&#xD;
          9. Total bilirubin &gt; 1.5 times the upper limit of normal unless the patient is Gilbert's&#xD;
             syndrome;&#xD;
&#xD;
         10. Partial thromboplastin time or activated partial thromboplastin time or international&#xD;
             normalized ratio &gt;1.5*ULN；in the absence of anticoagulant therapy;&#xD;
&#xD;
         11. There is an active infectious disease or any major infectious event requiring&#xD;
             high-level antibiotics;&#xD;
&#xD;
         12. Any condition that, in the opinion of the investigator, may increase the subject's&#xD;
             risk or interfere with the test results.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yi Zhang, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Affliated Hospital of Zhengzhou University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>He Huang, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Affliated Hospital of Zhejiang University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>First Affliated Hospital of Zhengzhou University</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>First Affliated Hospital of Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 19, 2017</study_first_submitted>
  <study_first_submitted_qc>July 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</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>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</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/NCT03229876
org study id: 2018CAR-00CH1
nct id: NCT03229876
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety and efficacy of ascending doses of
      CD19-UCART in patients with relapsed or refractory B-cell hematological malignancies.
CD19-UCART is a kind of "off-the-shelf" product originated from health donor's PBMC.This is a
      open-label, dose estilation study to evaluate the safety and anti-tumor efficacy of
      CD19-UCART in the treatment of relapsed or refractory B-cell hematological malignancies.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicities (DLTs) occurence
time frame: Baseline up to 35 days after T cell infusion
description: Adverse events assessed according to NCI-CTCAE v5.0 criteria
measure: Objective Response Rate
time frame: At 12 weeks, and overall
description: The total response rate after 90 days of treatment with study drug (overall response rate for ALL= CR+CRi; for NHL=CR+PR);
measure: Day 90 progression-free survival
time frame: Assessed up to 3 months
description: The 90-day progression-free survival rate following drug therapy.
measure: UCART cell survival time
time frame: up to 1 year after infusion
description: The number of UCART cells surviving in the body within 90 days after receiving the study drug;
measure: Progrssion-free survival
time frame: up to 2 years after infusion
description: The time from treatment with study drug to tumor progression or death.
measure: Overall survival
time frame: up to 2 years after infusion
description: the time from treatment with study drug to death by any cause.
arm group label: CD19-UCART
arm group type: Experimental
description: All patients will be treated with 1 injection of CD19-UCART. Three escalating dose-levels (1.0-2.0x10^6/kgBW, 2.5-5.0x10^6/kgBW, 5.5-10.0x10^6/kgBW) of CD19-UCART will be evaluated using a 3+3 design. Each CD19-UCART injection will be administered at Day 0.
intervention type: Biological
intervention name: CD19-UCART
description: A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.
arm group label: CD19-UCART
criteria: 
gender: All
minimum age: 1 Year
maximum age: 65 Years
healthy volunteers: No
last name: Yi Zhang, Professor
role: Principal Investigator
affiliation: First Affliated Hospital of Zhengzhou University
last name: He Huang, Professor
role: Principal Investigator
affiliation: First Affliated Hospital of Zhejiang University
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma, Non-Hodgkin
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
sharing ipd: No