<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/NCT03291444</url>
  </required_header>
  <id_info>
    <org_study_id>2017-XYNK-001</org_study_id>
    <nct_id>NCT03291444</nct_id>
  </id_info>
  <brief_title>CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS</brief_title>
  <official_title>A Clinical Study of Chimeric Antigen Receptor T Cells Combined With Eps8 Peptide Specific Dendritic Cell for Patients With Relapsed/Refractory Leukemia and Myelodysplastic Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhujiang Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Zhujiang Hospital</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>
      The main purpose of this study is to verify the safety and potential effectiveness of CART&#xD;
      cells combined with peptide specific dendritic cell in relapsed/refractory leukemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A prospective study to evaluate the safety and efficacy of Chimeric antigen receptor T cells&#xD;
      combined with Eps8 or WT1（Wilms tumor 1） peptide specific dendritic cell for patients with&#xD;
      relapsed/refractory leukemia. There are options for CAR-targets: CD19, CD20, CD22 and CD10&#xD;
      for acute lymphoblastic leukemia; CD33, CD38 CD56, CD117, CD123, CD34 and Muc1 for acute&#xD;
      myeloid leukemia and Myelodysplastic Syndrome. Progression free survival, overall Survival,&#xD;
      overall response rate, and duration of response were monitored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 23, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel 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, according to NCI CTCAE Version 4.0</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Incidence and severity of cytokine release syndrome(CRS): The systemic inflammatory response in patients with significantly increased IL-6 and other cytokines during the observation period is defined as CRS, which is divided into 1-5 grades, 1-2 Grade is mild, grade 3-5 is severe</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival time</measure>
    <time_frame>2 years</time_frame>
    <description>Time from random to the first occurrence of disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival time</measure>
    <time_frame>2 years</time_frame>
    <description>Time from randomization to death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>2 years</time_frame>
    <description>The proportion of the total number of patients with complete remission and partial remission (CR+PR) after treatment in the total number of evaluable cases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>2 years</time_frame>
    <description>During the observation period, the time between complete remission of bone marrow (the ratio of bone marrow blast cells is less than 5%) to the recurrence of bone marrow (the ratio of bone marrow blast cells is greater than 5%) is the continuous remission time.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Leukemia, Acute Lymphocytic (ALL)</condition>
  <condition>Leukemia, Acute Myelogenous (AML)</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>CAR-T cells combined with peptide specific dendritic cell</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CAR-T cells combined with Eps8 peptide specific dendritic cell,or CAR-T cells combined with WT1 peptide specific dendritic cell</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chimeric antigen receptor T cells</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After pretreatment, chimeric antigen receptor T cells will be transfused.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Chimeric antigen receptor T cells</intervention_name>
    <description>After pretreatment, chimeric antigen receptor T cells will be transfused.</description>
    <arm_group_label>CAR-T cells combined with peptide specific dendritic cell</arm_group_label>
    <arm_group_label>Chimeric antigen receptor T cells</arm_group_label>
    <other_name>CAR-T</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>peptide specific dendritic cell</intervention_name>
    <description>After transfusion of chimeric antigen receptor T cells, Eps8 or WT1 peptide specific dendritic cell were intradermal injected.</description>
    <arm_group_label>CAR-T cells combined with peptide specific dendritic cell</arm_group_label>
    <other_name>WT1 peptide specific dendritic cell</other_name>
    <other_name>Eps8 peptide specific dendritic cell</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Tumor type: Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)&#xD;
             according to the WHO criteria (at least 20% blasts in the marrow). All FAB subtypes&#xD;
             except M3. Patients with Myelodysplastic Syndrome, category of Refractory Anemia with&#xD;
             Excess Blasts (RAEB): RAEB I (WHO: medullary blast count ≤ 10% and a peripheral blast&#xD;
             count ≤ 5%) and RAEB II (WHO: medullary blast count &gt; 10% and/or &gt; 5% peripheral&#xD;
             blasts) can be included in the study in absence of other non-experimental treatment&#xD;
             modalities.&#xD;
&#xD;
          2. Positive antigen for any of CD19, CD20, CD22, CD10, CD33, CD38, CD56, CD117, CD123,&#xD;
             CD34, or Muc1.Simultaneously ,high expression of EPS8 or WT1 in acute leukemia.&#xD;
&#xD;
          3. Relapsed/Refractory leukemia patients：&#xD;
&#xD;
               -  Did not achieve complete remission after 2 times of standard plan chemotherapy.&#xD;
&#xD;
               -  Relapsed after first induction chemotherapy.&#xD;
&#xD;
               -  Did not response to chemotherapy before HSCT or relapsed after HSCT.&#xD;
&#xD;
               -  Cannot receive allo-HSCT or refuse to receive allo-HSCT.&#xD;
&#xD;
               -  Relapsed after CAR-T cell infusion.&#xD;
&#xD;
          4. Age greater than 18 year and less than 80 years.&#xD;
&#xD;
          5. Objectively assessable parameters of life expectancy: more than 3 months.&#xD;
&#xD;
          6. Performance status: WHO PS grade 0-1 (ECOG performance status 0 or 1).&#xD;
&#xD;
          7. Meet the following criteria for apheresis：WBC &gt;= 3,000/L, Hb &gt;= 8.0 g/dL, platelet&#xD;
             count &gt;= 80,000/mm3, &lt;= 600,000/mm3.&#xD;
&#xD;
          8. Pulmonary function: Peripheral blood oxygen saturation greater than 90%; Cardiac&#xD;
             function: Left ventricular ejection fraction &gt;60%.&#xD;
&#xD;
          9. Prior and concomitant associated diseases allowed with the exception of underlying&#xD;
             autoimmune disease and positive serology for HIV/HBV/HCV.&#xD;
&#xD;
         10. No concomitant use of immunosuppressive drugs.&#xD;
&#xD;
         11. Adequate renal and liver function, i.e. creatinin, bilirubin, and aminotransferase =&lt;&#xD;
             1.2 times the upper limit of normal.&#xD;
&#xD;
         12. Absence of any psychological, familial, sociological or geographical condition&#xD;
             potentially hampering compliance with the study protocol and follow-up schedule; those&#xD;
             conditions should be discussed with the patient before registration in the trial.&#xD;
&#xD;
         13. Women of child-bearing potential should use adequate contraception prior to study&#xD;
             entry and for the duration of study participation.&#xD;
&#xD;
         14. Written informed consent obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with severe complications: cardiovascular disorders, respiratory disorders,&#xD;
             renal dysfunction, immunodeficiency, hematological disorders, autoimmune diseases,&#xD;
             sever allergy and severe infectious disease.&#xD;
&#xD;
          2. Patients who should receive systemic administration of steroid or immunosuppressive&#xD;
             agents.&#xD;
&#xD;
          3. Presence of active brain metastases.&#xD;
&#xD;
          4. Pregnant, lactating, or possibly pregnant women, or willing to be pregnant.&#xD;
&#xD;
          5. Severe psychiatric disorder.&#xD;
&#xD;
          6. Active multiple cancers.&#xD;
&#xD;
          7. Patients have received other genetic therapy products.&#xD;
&#xD;
          8. Transfection efficiency was less than 30%.&#xD;
&#xD;
          9. Inappropriate for study entry judged by an attending physician.&#xD;
&#xD;
         10. patients who have sensitivity to drugs that provide local anesthesia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuhua Li, M.D, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhujiang Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sanfang Tu, M.D, Ph.D</last_name>
    <phone>86-20-62782322</phone>
    <email>doctortutu@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yanjie He, M.D, Ph.D</last_name>
    <phone>86-20-61643190</phone>
    <email>hyjgzh2006@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Zhujiang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510282</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sanfang Tu, M.D, Ph.D</last_name>
      <phone>86-20-62782322</phone>
      <email>doctortutu@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Yanjie He, M.D, Ph.D</last_name>
      <phone>86-20-61643190</phone>
      <email>hyjgzh2006@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Yuhua Li, M.D, Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>August 1, 2021</last_update_submitted>
  <last_update_submitted_qc>August 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2021</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>Leukemia</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Acute Disease</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/NCT03291444
org study id: 2017-XYNK-001
nct id: NCT03291444
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main purpose of this study is to verify the safety and potential effectiveness of CART
      cells combined with peptide specific dendritic cell in relapsed/refractory leukemia.
A prospective study to evaluate the safety and efficacy of Chimeric antigen receptor T cells
      combined with Eps8 or WT1（Wilms tumor 1） peptide specific dendritic cell for patients with
      relapsed/refractory leukemia. There are options for CAR-targets: CD19, CD20, CD22 and CD10
      for acute lymphoblastic leukemia; CD33, CD38 CD56, CD117, CD123, CD34 and Muc1 for acute
      myeloid leukemia and Myelodysplastic Syndrome. Progression free survival, overall Survival,
      overall response rate, and duration of response were monitored.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of study related adverse events, according to NCI CTCAE Version 4.0
time frame: up to 12 months
description: Incidence and severity of cytokine release syndrome(CRS): The systemic inflammatory response in patients with significantly increased IL-6 and other cytokines during the observation period is defined as CRS, which is divided into 1-5 grades, 1-2 Grade is mild, grade 3-5 is severe
measure: Progression free survival time
time frame: 2 years
description: Time from random to the first occurrence of disease progression.
measure: Overall survival time
time frame: 2 years
description: Time from randomization to death due to any cause
measure: Overall response rate
time frame: 2 years
description: The proportion of the total number of patients with complete remission and partial remission (CR+PR) after treatment in the total number of evaluable cases
measure: Duration of response
time frame: 2 years
description: During the observation period, the time between complete remission of bone marrow (the ratio of bone marrow blast cells is less than 5%) to the recurrence of bone marrow (the ratio of bone marrow blast cells is greater than 5%) is the continuous remission time.
arm group label: CAR-T cells combined with peptide specific dendritic cell
arm group type: Experimental
description: CAR-T cells combined with Eps8 peptide specific dendritic cell,or CAR-T cells combined with WT1 peptide specific dendritic cell
arm group label: Chimeric antigen receptor T cells
arm group type: Active Comparator
description: After pretreatment, chimeric antigen receptor T cells will be transfused.
intervention type: Biological
intervention name: Chimeric antigen receptor T cells
description: After pretreatment, chimeric antigen receptor T cells will be transfused.
arm group label: CAR-T cells combined with peptide specific dendritic cell
arm group label: Chimeric antigen receptor T cells
other name: CAR-T
intervention type: Biological
intervention name: peptide specific dendritic cell
description: After transfusion of chimeric antigen receptor T cells, Eps8 or WT1 peptide specific dendritic cell were intradermal injected.
arm group label: CAR-T cells combined with peptide specific dendritic cell
other name: WT1 peptide specific dendritic cell
other name: Eps8 peptide specific dendritic cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Yuhua Li, M.D, Ph.D
role: Principal Investigator
affiliation: Zhujiang Hospital
last name: Sanfang Tu, M.D, Ph.D
phone: 86-20-62782322
email: doctortutu@163.com
last name: Yanjie He, M.D, Ph.D
phone: 86-20-61643190
email: hyjgzh2006@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Myeloid, Acute
mesh term: Myelodysplastic Syndromes
mesh term: Acute Disease
sharing ipd: No