<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/NCT04447547</url>
  </required_header>
  <id_info>
    <org_study_id>1904B for NHL</org_study_id>
    <nct_id>NCT04447547</nct_id>
  </id_info>
  <brief_title>Clinical Trial of SL1904B CAR-T Cells for Relapsed or Refractory Non-Hodgkin Lymphoma</brief_title>
  <official_title>Clinical Trial of SL1904B CAR-T Cells for Relapsed or Refractory Non-Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hebei Senlang Biotechnology Inc., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beijing Lu Daopei Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hebei Yanda Ludaopei Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hebei Senlang Biotechnology Inc., Ltd.</source>
  <oversight_info>
    <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 study of patients with relapsed or refractory non-Hodgkin's lymphoma. To evaluate&#xD;
      the safety and efficacy of SL1904B in patients with relapsed or refractory non-Hodgkin's&#xD;
      lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The CARs consist of an anti-CD19 single-chain variable fragment（scFv） that was derived from&#xD;
      the FMC63 mouse hybridoma, a portion of the human CD137（4-1BB） molecule, and the&#xD;
      intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the&#xD;
      patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the&#xD;
      patients will be evaluated for adverse reactions and efficacy.&#xD;
&#xD;
      The Main research objectives:&#xD;
&#xD;
      To evaluate the safety and efficacy of SL1904B in patients with recurrent or refractory&#xD;
      non-Hodgkin's lymphoma&#xD;
&#xD;
      The Secondary research objectives:&#xD;
&#xD;
      To investigate the cytokinetic characteristics of SL1904B in patients with recurrent or&#xD;
      refractory non-Hodgkin's lymphoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2022</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Incidence and severity of adverse events</measure>
    <time_frame>First month post CAR-T cells infusion</time_frame>
    <description>To evaluate the possible adverse events occurred within first one month after SL1904B infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: Overall Remission Rate (ORR)</measure>
    <time_frame>3 months post CAR-T cells infusion</time_frame>
    <description>Overall Remission Rate (ORR) including partial remission and complete remission rate after infusion of SL1904B</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy:duration of response (DOR)</measure>
    <time_frame>24 months post CAR-T cells infusion</time_frame>
    <description>duration of response (DOR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: progression-free survival (PFS)</measure>
    <time_frame>24 months post CAR-T cells infusion</time_frame>
    <description>progression-free survival (PFS) time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CAR-T proliferation</measure>
    <time_frame>3 months post CAR-T cells infusion</time_frame>
    <description>the copy number of CD19 CAR- T cells in the genomes of PBMC by qPCR method and percentage of CD19 CAR- T cells measured by flow cytometry method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine release</measure>
    <time_frame>First month post CAR-T cells infusion</time_frame>
    <description>Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Non-hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>SL1904B CAR-T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with CD19 CAR-T cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD19 CAR-T</intervention_name>
    <description>Biological: CD19 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;</description>
    <arm_group_label>SL1904B CAR-T</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Sign the informed consent form and be willing and able to comply with the visit,&#xD;
             treatment regimen, laboratory examination and other requirements of the study as&#xD;
             stipulated in the trial flow chart;&#xD;
&#xD;
          2. The diagnosis of patients with relapsed or refractory non-hodgkin lymphoma;&#xD;
&#xD;
          3. There should be at least one measurable tumor focus according to the RECIST version&#xD;
             1.1;&#xD;
&#xD;
          4. ECOG Scores: 0~2;&#xD;
&#xD;
          5. The expression of CD19 on the tumor cells was reported as positive by either&#xD;
             immunohistochemistry or flow cytometry;&#xD;
&#xD;
          6. Estimated survival time was longer than 3 months;&#xD;
&#xD;
          7. main organ functions shall meet the following requirements including: serum creatinine&#xD;
             ≤1.5 times the upper limit of normal value (ULN); ALT ULN 2.5 or less; AST ULN 2.5 or&#xD;
             less; Total bilirubin ≤ 1.5ULN; Left ventricular ejection fraction (LVEF) ≥45%;&#xD;
             Hemoglobin ≥90g/L; Platelet count ≥50×109/L; absolute Neutrophil count (ANC)&#xD;
             ≥1.0×109/L; Blood oxygen saturation &gt;92%；&#xD;
&#xD;
          8. Peripheral blood mononuclear immune cells must be collected at least 2 weeks after the&#xD;
             last radiotherapy or systemic treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serious cardiac insufficiency；&#xD;
&#xD;
          2. Has a history of severe pulmonary function damaging;&#xD;
&#xD;
          3. With other tumors which is/are in advanced malignant and has/have systemic metastasis;&#xD;
&#xD;
          4. Merging the metabolic diseases (except diabetes);&#xD;
&#xD;
          5. Merging severe autoimmune diseases or immunodeficiency disease;&#xD;
&#xD;
          6. Patients with active hepatitis B or hepatitis C virus infection;&#xD;
&#xD;
          7. Patients with HIV infection or syphilis infection;&#xD;
&#xD;
          8. Has a history of serious allergies on Biological products (including antibiotics);&#xD;
&#xD;
          9. Participated in any other clinical drug trial for the last six months;&#xD;
&#xD;
         10. Being pregnant and lactating or having pregnancy within 12 months;&#xD;
&#xD;
         11. With other uncontrolled diseases and considered not suitable to participate by the&#xD;
             researchers;&#xD;
&#xD;
         12. Any situations that the researchers believe will increase the risks for the subject or&#xD;
             affect the results of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Lu Daopei Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <phone>008618611636172</phone>
    <email>peihua_lu@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jianqiang Li, PhD&amp;MD</last_name>
    <phone>008615511369555</phone>
    <email>limmune@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BeiJing Ludaopei Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Yizhuang</state>
        <zip>100000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <phone>008618611636172</phone>
      <email>peihua_lu@126.com</email>
    </contact>
    <investigator>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jianqiang Li, PhD&amp;MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>He bei Yan da Lu dao pei Hospital</name>
      <address>
        <city>Yanda</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peihua Lu</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>September 25, 2020</last_update_submitted>
  <last_update_submitted_qc>September 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NHL，CD19</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>
  <!-- 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/NCT04447547
org study id: 1904B for NHL
nct id: NCT04447547
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a study of patients with relapsed or refractory non-Hodgkin's lymphoma. To evaluate
      the safety and efficacy of SL1904B in patients with relapsed or refractory non-Hodgkin's
      lymphoma.
The CARs consist of an anti-CD19 single-chain variable fragment（scFv） that was derived from
      the FMC63 mouse hybridoma, a portion of the human CD137（4-1BB） molecule, and the
      intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the
      patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the
      patients will be evaluated for adverse reactions and efficacy.

      The Main research objectives:

      To evaluate the safety and efficacy of SL1904B in patients with recurrent or refractory
      non-Hodgkin's lymphoma

      The Secondary research objectives:

      To investigate the cytokinetic characteristics of SL1904B in patients with recurrent or
      refractory non-Hodgkin's lymphoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Incidence and severity of adverse events
time frame: First month post CAR-T cells infusion
description: To evaluate the possible adverse events occurred within first one month after SL1904B infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity
measure: Efficacy: Overall Remission Rate (ORR)
time frame: 3 months post CAR-T cells infusion
description: Overall Remission Rate (ORR) including partial remission and complete remission rate after infusion of SL1904B
measure: Efficacy:duration of response (DOR)
time frame: 24 months post CAR-T cells infusion
description: duration of response (DOR)
measure: Efficacy: progression-free survival (PFS)
time frame: 24 months post CAR-T cells infusion
description: progression-free survival (PFS) time
measure: CAR-T proliferation
time frame: 3 months post CAR-T cells infusion
description: the copy number of CD19 CAR- T cells in the genomes of PBMC by qPCR method and percentage of CD19 CAR- T cells measured by flow cytometry method
measure: Cytokine release
time frame: First month post CAR-T cells infusion
description: Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method
arm group label: SL1904B CAR-T
arm group type: Experimental
description: Patients will be treated with CD19 CAR-T cells
intervention type: Biological
intervention name: CD19 CAR-T
description: Biological: CD19 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;
arm group label: SL1904B CAR-T
criteria: 
gender: All
minimum age: 3 Years
maximum age: 70 Years
healthy volunteers: No
last name: Peihua Lu, PhD&MD
role: Principal Investigator
affiliation: Beijing Lu Daopei Hospital
last name: Peihua Lu, PhD&MD
phone: 008618611636172
email: peihua_lu@126.com
last name: Jianqiang Li, PhD&MD
phone: 008615511369555
email: limmune@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin