xml: <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/NCT05978661</url>
    </required_header>
    <id_info>
      <org_study_id>NJCT-2301</org_study_id>
      <nct_id>NCT05978661</nct_id>
    </id_info>
    <brief_title>FKC288 for Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis</brief_title>
    <official_title>A Single-Center Exploratory Study to Evaluate the Safety and Efficacy of FKC288 in Subjects With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Nanjing University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Nanjing University School of Medicine</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 study is a single-center exploratory clinical trial. It is estimated that 6-12 subjects&#xD;
        will be enrolled. The &quot;BOIN&quot; dose escalation design is adopted. The main purpose is to&#xD;
        evaluate the safety of FKC288 in the treatment of subjects with relapsed or refractory AL&#xD;
        amyloidosis and explore the recommended phase II dose of FKC288 in the treatment of patients&#xD;
        with relapsed/refractory systemic Light Chain (AL) amyloidosis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A leukapheresis procedure will be performed to manufacture FKC288 chimeric antigen receptor&#xD;
        (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and&#xD;
        lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for&#xD;
        three consecutive days. After 1-day rest, subjects will receive a single dose infusion of&#xD;
        FKC288 at 0.1, 0.3, 1.0, or 3.0x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study&#xD;
        for a minimum of 2 years after FKC288 infusion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">June 2026</completion_date>
    <primary_completion_date type="Anticipated">June 2025</primary_completion_date>
    <phase>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>The proportion of subjects with dose-limiting toxicity</measure>
      <time_frame>Within 28 days after FKC288 injection infusion</time_frame>
      <description>The number of participants with dose limiting toxicity in each dose group and the type of dose limiting toxicity that occurred.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>The proportion of subjects with adverse events</measure>
      <time_frame>Within 24 weeks after FKC288 injection infusion</time_frame>
      <description>All adverse events were evaluated according to NCI-CTCAE v5.0 criteria.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects achieving hematologic response</measure>
      <time_frame>Within 6 months after FKC288 injection infusion</time_frame>
      <description>The proportion of subjects who achieve any type of hematologic response according to the 2023 National Comprehensive Cancer Network (NCCN) systemic light-chain amyloidosis guidelines within 6 months after receiving FKC288 infusion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects achieving organ response</measure>
      <time_frame>Within 2 years after FKC288 injection infusion</time_frame>
      <description>The proportion of subjects who achieve any type of organ response according to the 2023 National Comprehensive Cancer Network (NCCN) systemic light-chain amyloidosis guidelines within 2 years after receiving FKC288 infusion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS) of all subjects</measure>
      <time_frame>Within 2 years after FKC288 injection infusion</time_frame>
      <description>Time from the first FKC288 infusion to the first assessment of disease progression/relapse or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS) of all subjects</measure>
      <time_frame>Within 2 years after FKC288 injection infusion</time_frame>
      <description>Time from the first FKC288 infusion to death from any cause.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Light Chain Amyloidosis</condition>
    <arm_group>
      <arm_group_label>Treatment arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>FKC288</intervention_name>
      <description>Administration of FKC288 Four dose groups of 0.1×10^6 CAR-T/kg, 0.3×10^6 CAR-T/kg, 1.0×10^6 CAR-T/kg, and 3.0×10^6 CAR-T/kg FKC288 are designed in this study. 3 to 6 subjects are expected to be enrolled in each dose group according to observed DLT.</description>
      <arm_group_label>Treatment arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. The subject must personally sign a written informed consent form approved by the&#xD;
               ethics committee before the start of the study;&#xD;
  &#xD;
            2. The subject's age is ≥18 years old and &lt;70 years old;&#xD;
  &#xD;
            3. The subject must be diagnosed with light chain amyloidosis by pathological&#xD;
               examination, with at least one major organ involved (heart, kidney, or liver);&#xD;
  &#xD;
            4. The subject with recurrent/refractory light chain amyloidosis that achieved no&#xD;
               response with conventional treatment;&#xD;
  &#xD;
            5. dFLC &gt; 50mg/L;&#xD;
  &#xD;
            6. Expected survival ≥ 12 weeks;&#xD;
  &#xD;
            7. ECOG score ≤ 2 points;&#xD;
  &#xD;
            8. Female subjects with fertility should agree to practice an effective method of&#xD;
               contraception from the day of signing the ICF until 365 days after the infusion. An&#xD;
               effective method of contraception is defined as abstinence or contraceptive methods&#xD;
               with an annual failure rate of &lt;1% specified in the plan.&#xD;
  &#xD;
            9. Before enrollment, the subject must have appropriate organ function and meet all the&#xD;
               following criteria:&#xD;
  &#xD;
          1) Absolute neutrophil count ≥ 1.0×109/L (use of granulocyte colony-stimulating factor&#xD;
          (G-CSF) support is allowed, but must be without supportive treatment within 7 days before&#xD;
          the examination); 2) Platelet count ≥ 75×109/L (no transfusion support [including component&#xD;
          transfusion] or treatments aimed at raising platelets such as thrombopoietin [TPO] should&#xD;
          be received within 7 days before the examination); 3) Hemoglobin ≥ 9 g/dl (no transfusion&#xD;
          support [including component transfusion] should be received within 7 days before the&#xD;
          examination); 4) Bilirubin value ≤ 1.5× upper limit of normal (ULN) (except bile duct&#xD;
          obstruction caused by tumor compression); 5) Creatinine clearance rate ≥ 40 ml/min; 6) ALT&#xD;
          or AST ≤ 2.5× ULN (≤5 times the upper limit of normal in patients with liver involvement);&#xD;
          7) Echocardiography results indicate left ventricular ejection fraction ≥ 50% with no&#xD;
          significant pericardial effusion; 8) NTproBNP &lt; 1800pg/ml, TNT &lt; 0.06ng/ml; 9) Stable&#xD;
          coagulation function: INR ≤ 1.5, APTT ≤ 1.2× ULN (excluding tumor-related anticoagulant&#xD;
          therapy); 10) &gt;95% basic blood oxygen saturation in the natural indoor air environments.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects who have received any of the following treatments prior to enrollment: 1)&#xD;
               Subjects who have received gene therapy before enrollment; 2) Subjects who have&#xD;
               received live vaccines within 4 weeks prior to enrollment; 3) Subjects has received&#xD;
               other interventional clinical research drugs within 12 weeks before apheresis.&#xD;
  &#xD;
            2. Subjects with central metastasis or complete intestinal obstruction.&#xD;
  &#xD;
            3. Subject with moderate or more severe hydrothorax and ascites which are hard to control&#xD;
               by conventional treatment and require continuous catheter drainage.&#xD;
  &#xD;
            4. With an active malignant tumor in the past 5 years, unless it is a curable tumor and&#xD;
               has been obviously cured.&#xD;
  &#xD;
            5. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core&#xD;
               antibody (HBcAb) and have abnormal peripheral blood HBV DNA test results (HBV DNA test&#xD;
               abnormality is defined as HBV DNA quantitative detection is higher than the detection&#xD;
               center's detection lower limit or higher than the detection center's normal reference&#xD;
               range or HBV DNA qualitative detection is positive); hepatitis C virus (HCV) antibody&#xD;
               positive and peripheral blood hepatitis C virus (HCV) RNA positive; human&#xD;
               immunodeficiency virus (HIV) antibody positive; the cytomegalovirus (CMV) DNA&#xD;
               positive; syphilis testing RPR positive.&#xD;
  &#xD;
            6. Presence of uncontrollable active infections (excluding &lt;CTCAE grade 2 urinary and&#xD;
               respiratory tract infections).&#xD;
  &#xD;
            7. Severe cardiovascular diseases, including but not limited to unstable angina pectoris,&#xD;
               myocardial infarction (within 6 months prior to screening), congestive heart failure&#xD;
               (New York Heart Association [NYHA] classification ≥ III), and severe arrhythmias.&#xD;
  &#xD;
            8. Subjects with hypertension that cannot be controlled by medication.&#xD;
  &#xD;
            9. Toxicity reactions that have not been relieved to baseline or ≤ grade 1 (NCI-CTCAE&#xD;
               version 5.0, except for hair loss and laboratory test abnormalities without clinical&#xD;
               significance) from past treatments.&#xD;
  &#xD;
           10. Major surgery within 2 weeks before enrollment, or has a surgery planned during the&#xD;
               time the subject is expected to be infused with FKC288 or within 12 weeks after FKC288&#xD;
               infusion (except planned surgery under local anesthesia).&#xD;
  &#xD;
           11. Subject who has a solid organ transplant.&#xD;
  &#xD;
           12. Women who are pregnant or breastfeeding.&#xD;
  &#xD;
           13. Subjects with previous central nervous system diseases (such as cerebral aneurysm,&#xD;
               epilepsy, stroke, dementia, psychosis, etc.) or conscious disorders.&#xD;
  &#xD;
           14. Other systemic diseases that the investigator judges as unstable, including but not&#xD;
               limited to severe liver, kidney, or metabolic diseases that require medication.&#xD;
  &#xD;
           15. Known life-threatening allergic reactions, hypersensitivity reactions, or intolerance&#xD;
               to FKC288 cell preparations or their components.&#xD;
  &#xD;
           16. Subjects judged by the investigator to have bleeding or severe thrombosis, or have&#xD;
               inherited/acquired bleeding and severe thrombosis (including hemophilia, coagulation&#xD;
               dysfunction, thrombocytopenia, splenomegaly, etc.), or are receiving thrombolysis or&#xD;
               anticoagulation therapy.&#xD;
  &#xD;
           17. Other situations deemed inappropriate for inclusion by the investigator.&#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_contact>
      <last_name>Xianghua Huang, MD</last_name>
      <phone>86-25-80862002</phone>
      <email>hxhszb@163.com</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>May 7, 2023</study_first_submitted>
    <study_first_submitted_qc>July 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>July 30, 2023</last_update_submitted>
    <last_update_submitted_qc>July 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Nanjing University School of Medicine</investigator_affiliation>
      <investigator_full_name>Zhi-Hong Liu, MD</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>AL Amyloidosis</keyword>
    <keyword>BCMA/CD19-CAR-T cell</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Amyloidosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05978661
  org study id: NJCT-2301
  nct id: NCT05978661
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study is a single-center exploratory clinical trial. It is estimated that 6-12 subjects
        will be enrolled. The "BOIN" dose escalation design is adopted. The main purpose is to
        evaluate the safety of FKC288 in the treatment of subjects with relapsed or refractory AL
        amyloidosis and explore the recommended phase II dose of FKC288 in the treatment of patients
        with relapsed/refractory systemic Light Chain (AL) amyloidosis.
  A leukapheresis procedure will be performed to manufacture FKC288 chimeric antigen receptor
        (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and
        lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for
        three consecutive days. After 1-day rest, subjects will receive a single dose infusion of
        FKC288 at 0.1, 0.3, 1.0, or 3.0x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study
        for a minimum of 2 years after FKC288 infusion.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The proportion of subjects with dose-limiting toxicity
  time frame: Within 28 days after FKC288 injection infusion
  description: The number of participants with dose limiting toxicity in each dose group and the type of dose limiting toxicity that occurred.
  measure: The proportion of subjects with adverse events
  time frame: Within 24 weeks after FKC288 injection infusion
  description: All adverse events were evaluated according to NCI-CTCAE v5.0 criteria.
  measure: Proportion of subjects achieving hematologic response
  time frame: Within 6 months after FKC288 injection infusion
  description: The proportion of subjects who achieve any type of hematologic response according to the 2023 National Comprehensive Cancer Network (NCCN) systemic light-chain amyloidosis guidelines within 6 months after receiving FKC288 infusion.
  measure: Proportion of subjects achieving organ response
  time frame: Within 2 years after FKC288 injection infusion
  description: The proportion of subjects who achieve any type of organ response according to the 2023 National Comprehensive Cancer Network (NCCN) systemic light-chain amyloidosis guidelines within 2 years after receiving FKC288 infusion.
  measure: Progression-free survival (PFS) of all subjects
  time frame: Within 2 years after FKC288 injection infusion
  description: Time from the first FKC288 infusion to the first assessment of disease progression/relapse or death from any cause.
  measure: Overall survival (OS) of all subjects
  time frame: Within 2 years after FKC288 injection infusion
  description: Time from the first FKC288 infusion to death from any cause.
  arm group label: Treatment arm
  arm group type: Experimental
  intervention type: Drug
  intervention name: FKC288
  description: Administration of FKC288 Four dose groups of 0.1×10^6 CAR-T/kg, 0.3×10^6 CAR-T/kg, 1.0×10^6 CAR-T/kg, and 3.0×10^6 CAR-T/kg FKC288 are designed in this study. 3 to 6 subjects are expected to be enrolled in each dose group according to observed DLT.
  arm group label: Treatment arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Xianghua Huang, MD
  phone: 86-25-80862002
  email: hxhszb@163.com
  responsible party type: Principal Investigator
  investigator affiliation: Nanjing University School of Medicine
  investigator full name: Zhi-Hong Liu, MD
  investigator title: Professor
  mesh term: Amyloidosis
  sharing ipd: No