<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/NCT03840317</url>
  </required_header>
  <id_info>
    <org_study_id>Senl_1904A &amp; Senl_1904B CAR-T</org_study_id>
    <nct_id>NCT03840317</nct_id>
  </id_info>
  <brief_title>Senl_1904A and Senl_1904B Chimeric Antigen Receptor （CAR） T-Cell in the Treatment of r/ r Acute B Lymphocytic Leukemia</brief_title>
  <official_title>Randomized, Parallel-arm, Controlled Trial of Senl_1904A and Senl_1904B Autologous CAR-T Cell Injections in the Treatment of Relapsed and Refractory Acute B Lymphocytic Leukemia(r/r B-ALL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hebei Senlang Biotechnology Inc., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <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 an open, two arms, mask phase I clinical study to evaluate efficacy and safety of two&#xD;
      different chimeric antigen receptor T cell immunotherapies (Senl_1904A and Senl_1904B)&#xD;
      targeting cluster of differentiation antigen 19 （CD19） in the treatment of Acute lymphocytic&#xD;
      Leukemia. A total of 20 patients are planned to be enrolled following up half a year.&#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. Autologous T cells will be gene&#xD;
      engineered with the CAR gene using a lentivirus vector. Compared to Senl_1904A, Senl_1904B&#xD;
      has a higher and more stable transfection efficiency and secretes lower levels of cytokines&#xD;
      in functional assays, thus having the potential to significantly reduce the incidence of&#xD;
      serious adverse events while ensuring the same complete response rate. Prior to T cell&#xD;
      infusion, the patients will be subjected to preconditioning treatment. After T cell infusion,&#xD;
      the patients will be evaluated for one month after infusion for adverse reactions and&#xD;
      efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 2, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor load</measure>
    <time_frame>up to one month</time_frame>
    <description>Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CAR T cell expansion</measure>
    <time_frame>up to one month</time_frame>
    <description>The percentage of CAR-T cells (CAR+/CD3+ T cells) in the bone marrow samples, quantified by flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CAR T cell persistence</measure>
    <time_frame>up to one month</time_frame>
    <description>The method to detect CAR-T cell persistence is by determining the exact copies of CAR per ug DNA in BM through quantitative polymerase chain reaction（qPCR）</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Acute Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Senl_1904A CD19 CAR-T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous CD19-targeting CAR T cells, dosage 3*10^5/kg, intravenous injection once</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Senl_1904B CD19 CAR-T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous CD19-targeting CAR T cells,dosage 3*10^5/kg, intravenous injection once</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous CD19-targeting CAR T cells</intervention_name>
    <description>Autologous CD19-targeting CAR T cells</description>
    <arm_group_label>Senl_1904A CD19 CAR-T</arm_group_label>
    <arm_group_label>Senl_1904B CD19 CAR-T</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with acute lymphocytic leukemia who voluntarily signed informed consent and&#xD;
             met the following criteria:&#xD;
&#xD;
               1. Patients with relapsed and refractory acute B lymphocytic leukemia with any of&#xD;
                  the following:&#xD;
&#xD;
                    1. Recurrence after remission by chemotherapy or autologous stem cell&#xD;
                       transplantation (including B-ALL patients with bone marrow recurrence of&#xD;
                       morphology and recurrence of micro-residual );&#xD;
&#xD;
                    2. Primary B-ALL patients who cannot be completely relieved by repeated&#xD;
                       chemotherapy twice or more;&#xD;
&#xD;
                    3. High-risk initial onset B-ALL patients not completely relieved after 1 or 2&#xD;
                       times of chemotherapy but not suitable for re-chemotherapy ;&#xD;
&#xD;
               2. Tumor cells confirmed CD19 positive by Flow cytometry (FCM)&#xD;
&#xD;
               3. For B-ALL patients with simple extramedullary recurrence , there must be at least&#xD;
                  one evaluable lesion;&#xD;
&#xD;
               4. Eastern Cooperative Oncology Group (ECOG) ≤ 2 points;&#xD;
&#xD;
               5. Age 3 - 65 years old;&#xD;
&#xD;
               6. The bone marrow tumor load value (morphology) &gt; 5% at the time of enrollment;&#xD;
&#xD;
               7. The main organ function needs to meet the above conditions: cardiac ultrasound or&#xD;
                  multiple gated image acquisition analysis （MUGA） scan indicate the cardiac&#xD;
                  ejection fraction is ≥50% , and there is no obvious abnormality in the&#xD;
                  electrocardiogram; blood oxygen saturation≥90%; creatinine ≤1.6mg/dl; alanine&#xD;
                  amino transferase (ALT) and Aspartate transaminase (AST)≤3 times normal range,&#xD;
                  total bilirubin（TBil） ≤2.0mg/dl;&#xD;
&#xD;
               8. The expected survival time is longer than 3 months;&#xD;
&#xD;
               9. The pregnancy test for women of childbearing age must be negative; Subjects with&#xD;
                  a pregnancy plan must agree to take contraception before the enrollment study and&#xD;
                  after the study lasts for one year; if the subject is pregnant or suspects of&#xD;
                  pregnancy, the investigator should be notified immediately&#xD;
&#xD;
              10. An informed consent form is required.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) Severe cardiac insufficiency; 2) A history of severe pulmonary dysfunction; 3)&#xD;
             Combined with other malignant tumors; 4) Combined with serious infections or&#xD;
             persistent infection and cannot be effectively controlled; 5) Combined with metabolic&#xD;
             diseases (except DM); 6) Combined with severe autoimmune diseases or congenital immune&#xD;
             defects; 7) Active hepatitis (HBV DNA or HCVRNA detection positive); 8) HIV infection&#xD;
             or syphilis infection; 9) A history of severe allergies to biological products&#xD;
             (including antibiotics); 10) Subjects with recurrence after allogeneic hematopoietic&#xD;
             stem cell transplantation 11) chronic lymphocytic leukemia（CLL） /myeloproliferative&#xD;
             neoplasms with acute lymphoid transformation or CLL transform to ALL ; 12) Any drug&#xD;
             that has been used against graft-versus-host disease（GVHD） for nearly 4 weeks, such as&#xD;
             methotrexate or other chemotherapeutic drugs, mycophenolate mofetil, immunosuppressive&#xD;
             antibodies, etc.; 13) Subjects who have received any anti-CD19 medication; 14)&#xD;
             Subjects who have used anti-cluster of differentiation antigen 20（CD20） drugs (such as&#xD;
             rituximab) for nearly 4 weeks; 15) Subjects who have participated in any other&#xD;
             clinical drug trials in the past six months; 16) Female patients who are pregnant and&#xD;
             lactating, or have a pregnancy plan within 12 months; 17) The investigator believes&#xD;
             that it may increase the risk of the subject or interfere with the outcome of the test&#xD;
             (with a history of severe mental illness, drug abuse and history of addiction).&#xD;
&#xD;
        Exit criteria：&#xD;
&#xD;
          1. The subjects request to withdraw from the study before CAR-T infusion&#xD;
&#xD;
          2. The subjects seriously violate the protocol&#xD;
&#xD;
          3. Before CAR-T infusion, the following indicators are still abnormal after treatment:&#xD;
&#xD;
             Platelets &lt;20x10^9/L, hemoglobin ≤80g/L, peripheral finger oxygen &lt;90%, AST / ALT /&#xD;
             alkaline phosphatase（ALP） ≥ 2.5 upper limits of normal（ULN）, total bilirubin ≥ 1.5ULN&#xD;
             , creatinine clearance rate &lt;70ml / min, left ventricular ejection fraction &lt;50%, the&#xD;
             researcher judged that the test needs to be terminated early;&#xD;
&#xD;
          4. The therapeutic dose of steroids was not stopped within 72 hours prior to CAR-T&#xD;
             infusion and the investigator determined that the trial needs to be terminated .&#xD;
             However, the following physiologically acceptable doses of steroids are permissible:&#xD;
             hydrocortisone or equivalent &lt;6-12 mg/m2/day ;&#xD;
&#xD;
          5. Not enough T cells for manufacture standard CAR-T cells&#xD;
&#xD;
          6. Other serious adverse events occurred&#xD;
&#xD;
          7. MRD become negative after preconditioning regiment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>65 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>Hebei Yanda Ludaopei Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hebei Yanda Ludaopei Hospital</name>
      <address>
        <city>Langfang</city>
        <state>Hebei</state>
        <zip>065000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>January 27, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>January 18, 2021</last_update_submitted>
  <last_update_submitted_qc>January 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 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>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, B-Cell</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/NCT03840317
org study id: Senl_1904A & Senl_1904B CAR-T
nct id: NCT03840317
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is an open, two arms, mask phase I clinical study to evaluate efficacy and safety of two
      different chimeric antigen receptor T cell immunotherapies (Senl_1904A and Senl_1904B)
      targeting cluster of differentiation antigen 19 （CD19） in the treatment of Acute lymphocytic
      Leukemia. A total of 20 patients are planned to be enrolled following up half a year.
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. Autologous T cells will be gene
      engineered with the CAR gene using a lentivirus vector. Compared to Senl_1904A, Senl_1904B
      has a higher and more stable transfection efficiency and secretes lower levels of cytokines
      in functional assays, thus having the potential to significantly reduce the incidence of
      serious adverse events while ensuring the same complete response rate. Prior to T cell
      infusion, the patients will be subjected to preconditioning treatment. After T cell infusion,
      the patients will be evaluated for one month after infusion for adverse reactions and
      efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Tumor load
time frame: up to one month
description: Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
measure: CAR T cell expansion
time frame: up to one month
description: The percentage of CAR-T cells (CAR+/CD3+ T cells) in the bone marrow samples, quantified by flow cytometry.
measure: CAR T cell persistence
time frame: up to one month
description: The method to detect CAR-T cell persistence is by determining the exact copies of CAR per ug DNA in BM through quantitative polymerase chain reaction（qPCR）
arm group label: Senl_1904A CD19 CAR-T
arm group type: Experimental
description: Autologous CD19-targeting CAR T cells, dosage 3*10^5/kg, intravenous injection once
arm group label: Senl_1904B CD19 CAR-T
arm group type: Experimental
description: Autologous CD19-targeting CAR T cells,dosage 3*10^5/kg, intravenous injection once
intervention type: Biological
intervention name: Autologous CD19-targeting CAR T cells
description: Autologous CD19-targeting CAR T cells
arm group label: Senl_1904A CD19 CAR-T
arm group label: Senl_1904B CD19 CAR-T
criteria: 
gender: All
minimum age: 3 Years
maximum age: 65 Years
healthy volunteers: No
last name: Peihua Lu, PhD&MD
role: Principal Investigator
affiliation: Hebei Yanda Ludaopei Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, B-Cell