<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/NCT03790891</url>
  </required_header>
  <id_info>
    <org_study_id>2018-127</org_study_id>
    <nct_id>NCT03790891</nct_id>
  </id_info>
  <brief_title>Treatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy</brief_title>
  <official_title>Adoptive Immunotherapy for Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Timmune Biotech Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Timmune Biotech Inc.</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>
      This is a single arm, open-label, early phase Ⅰ study, to determine the safety and efficacy&#xD;
      of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the&#xD;
      CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Non-Hodgkin&#xD;
      lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and&#xD;
      expansion, thus make it a tri-functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous&#xD;
      tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR-NK&#xD;
      cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for&#xD;
      CD19-TriCAR-SILK therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 5, 2019</start_date>
  <completion_date type="Anticipated">January 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2021</primary_completion_date>
  <phase>Early 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>safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence of treatment-related adverse events as assessed by CTCAE v4.03</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)</measure>
    <time_frame>24 months</time_frame>
    <description>Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）</measure>
    <time_frame>24 months</time_frame>
    <description>Partial response rate per the revised International Working Group (IWG) Response Criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response （The time from response to relapse or progression）</measure>
    <time_frame>24 months</time_frame>
    <description>The time from response to relapse or progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival （The time from the first day of treatment to the date on which disease progresses）</measure>
    <time_frame>24 months</time_frame>
    <description>The time from the first day of treatment to the date on which disease progresses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival （The number of patient alive, with or without signs of cancer）</measure>
    <time_frame>24 months</time_frame>
    <description>The number of patient alive, with or without signs of cancer</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>CD19-TriCAR-T/SILK</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CD19-TriCAR-T/SILK cells will be administered intravenously</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD19-TriCAR-T/SILK</intervention_name>
    <description>A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells.</description>
    <arm_group_label>CD19-TriCAR-T/SILK</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All subjects must personally sign and date the consent form before initiating any&#xD;
             study specific procedures or activities;&#xD;
&#xD;
          2. All subjects must be able to comply with all the scheduled procedures in the study;&#xD;
&#xD;
          3. Refractory or relapsed malignant Non-Hodgkin lymphoma, defined as one or more of the&#xD;
             following: Relapsed in 6 months after most recent therapy; Progressive disease in&#xD;
             standard chemotherapy; Disease progression or relapsed in ≤12 months of ASCT;&#xD;
&#xD;
          4. At least one measurable lesion per revised IWG Response Criteria;&#xD;
&#xD;
          5. Aged &lt;70 years;&#xD;
&#xD;
          6. Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance&#xD;
             status of≤2;&#xD;
&#xD;
          7. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped&#xD;
             for more than 4 weeks;&#xD;
&#xD;
          8. All other treatment induced adverse events must have been resolved to ≤grade 1;&#xD;
&#xD;
          9. Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB&gt;70g/L,&#xD;
             Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN,&#xD;
             Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of fungal, bacterial, viral, or other infection that is hardly to&#xD;
             control（defined by investigator）;&#xD;
&#xD;
          2. Patients with symptomatic central nervous system metastasis, intracranial metastasis,&#xD;
             and cancer cells found in cerebrospinal fluid are not recommended to participate in&#xD;
             this study. Symptom free or post-treatment stable disease or disappearance of lesions&#xD;
             should not be excluded. The specific selection is ultimately determined by the&#xD;
             investigator;&#xD;
&#xD;
          3. Lactating women or women of childbearing age who plan to conceive during the time&#xD;
             period;&#xD;
&#xD;
          4. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV&#xD;
             positive);&#xD;
&#xD;
          5. Known history of infection with HIV;&#xD;
&#xD;
          6. Subjects need systematic usage of corticosteroid;&#xD;
&#xD;
          7. Subjects need systematic usage of immunosuppressive drug;&#xD;
&#xD;
          8. Planed operation, history of other related disease, or any other related laboratory&#xD;
             tests restrict patients for the study;&#xD;
&#xD;
          9. Other reasons the investigator consider the patient may not be suitable for the study.&#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_official>
    <last_name>Yao Hongxia</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hainan General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yao Hongxia</last_name>
    <phone>+86 13876081106</phone>
    <email>yaohongxia768@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gao Bin</last_name>
    <phone>+86 13910899150</phone>
    <email>bin.gaoa@timmune.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hainan Cancer Hospital</name>
      <address>
        <city>Haikou</city>
        <state>Hainan</state>
        <zip>570100</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuyang Tian</last_name>
      <phone>+86 18686853849</phone>
      <email>tianyuyang@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hainan General Hospital</name>
      <address>
        <city>Haikou</city>
        <state>Hainan</state>
        <zip>570100</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yao Hongxia</last_name>
      <phone>+86 13876081106</phone>
      <email>yaohongxia768@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Wu Yasong</last_name>
      <phone>+86 18020091931</phone>
      <email>yasong.wu@timmune.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Hainan Medical University</name>
      <address>
        <city>Haikou</city>
        <state>Hainan</state>
        <zip>570100</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Haifeng Lin</last_name>
      <phone>+86 13322060949</phone>
      <email>13322060949@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. doi: 10.1016/j.ymthe.2016.10.020. Epub 2017 Jan 4.</citation>
    <PMID>28129122</PMID>
  </reference>
  <reference>
    <citation>Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.</citation>
    <PMID>28925994</PMID>
  </reference>
  <reference>
    <citation>Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y. Erratum In: J Hematol Oncol. 2018 Jun 13;11(1):81.</citation>
    <PMID>29499750</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>December 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>March 11, 2020</last_update_submitted>
  <last_update_submitted_qc>March 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CAR-T</keyword>
  <keyword>TriCAR-T</keyword>
  <keyword>CD19-TriCAR-T</keyword>
  <keyword>CD19-TriCAR-SILK</keyword>
  <keyword>Non-Hodgkin Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</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/NCT03790891
org study id: 2018-127
nct id: NCT03790891
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single arm, open-label, early phase Ⅰ study, to determine the safety and efficacy
      of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment.
CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the
      CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Non-Hodgkin
      lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and
      expansion, thus make it a tri-functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous
      tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR-NK
      cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for
      CD19-TriCAR-SILK therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
time frame: 24 months
description: Incidence of treatment-related adverse events as assessed by CTCAE v4.03
measure: Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
time frame: 24 months
description: Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
measure: Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
time frame: 24 months
description: Partial response rate per the revised International Working Group (IWG) Response Criteria
measure: Duration of Response （The time from response to relapse or progression）
time frame: 24 months
description: The time from response to relapse or progression
measure: Progression Free Survival （The time from the first day of treatment to the date on which disease progresses）
time frame: 24 months
description: The time from the first day of treatment to the date on which disease progresses
measure: Overall Survival （The number of patient alive, with or without signs of cancer）
time frame: 24 months
description: The number of patient alive, with or without signs of cancer
arm group label: CD19-TriCAR-T/SILK
arm group type: Experimental
description: CD19-TriCAR-T/SILK cells will be administered intravenously
intervention type: Biological
intervention name: CD19-TriCAR-T/SILK
description: A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells.
arm group label: CD19-TriCAR-T/SILK
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yao Hongxia
role: Principal Investigator
affiliation: Hainan General Hospital
last name: Yao Hongxia
phone: +86 13876081106
email: yaohongxia768@163.com
last name: Gao Bin
phone: +86 13910899150
email: bin.gaoa@timmune.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: China
citation: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. doi: 10.1016/j.ymthe.2016.10.020. Epub 2017 Jan 4.
PMID: 28129122
citation: Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
PMID: 28925994
citation: Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y. Erratum In: J Hematol Oncol. 2018 Jun 13;11(1):81.
PMID: 29499750
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
sharing ipd: No