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/NCT06005649</url>
    </required_header>
    <id_info>
      <org_study_id>HY004102</org_study_id>
      <nct_id>NCT06005649</nct_id>
    </id_info>
    <brief_title>Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma</brief_title>
    <official_title>A Multi-center, Open Label, Single-arm, Phase I/II Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Juventas Cell Therapy Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Juventas Cell Therapy Ltd.</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 multi-center, open-label, single-arm, phase I/II trial to evaluate the safety and&#xD;
        efficacy of HY004 treatment in Adult patients with relapsed or refractory B-cell&#xD;
        Non-Hodgkin's Lymphoma (r/r B-NHL).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This trial is a multi-center, open label, single-arm, phase I/II trial to evaluate the safety&#xD;
        and efficacy of HY004 in Adult(aged 18~75 years old) patients with r/r B-NHL.&#xD;
  &#xD;
        The phase I part of the trial is to evaluate the safety, optimal dose of HY004,&#xD;
        Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Adult&#xD;
        patients with r/r B-NHL. The phase II part of the trial is to evaluate the efficacy and&#xD;
        safety of HY004 in in the treatment of Adult patients with r/r B-NHL. The study includes&#xD;
        screening, pre-treatment (Cell Product manufacture &amp; lymphodepletion), HY004 infusion ,&#xD;
        safety and efficacy follow-up, and survival follow-up. All subjects who have received HY004&#xD;
        infusion will be followed for up to 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">September 2026</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</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>【Phase I】Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)</measure>
      <time_frame>28 days</time_frame>
      <description>Determine the MTD and DLT of HY004 in the Treatment and recommend the dose for Phase II study.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)</measure>
      <time_frame>3 months</time_frame>
      <description>Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>【Phase I】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)</measure>
      <time_frame>3 months</time_frame>
      <description>Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety of CNCT19 therapy: CTCAE v5.0</measure>
      <time_frame>24 months</time_frame>
      <description>Safety measures include adverse events as assessed by CTCAE v5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complete Remission Rate (CRR)</measure>
      <time_frame>3 months</time_frame>
      <description>Efficacy of HY004 as measured by CR at 3 months after HY004 Cell Injection infusion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ORR（CR+PR）/CRR</measure>
      <time_frame>28 days</time_frame>
      <description>Efficacy of HY004 as measured by ORR/CRR at 28 days after cell infusion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ORR（CR+PR）/CRR</measure>
      <time_frame>6 months</time_frame>
      <description>Efficacy of HY004 as measured by ORR/CRR at 6 months after cell infusion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Best Overall Response (BOR)</measure>
      <time_frame>24 mouths</time_frame>
      <description>The best overall response after HY004 infusion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Remission (DOR)</measure>
      <time_frame>24 mouths</time_frame>
      <description>DOR means the duration from reaching the response (e.g., CR or PR) criteria of the therapy to the first, clearly defined progressive disease, or death for disease under investigation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>24 mouths</time_frame>
      <description>PFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, or death for any reason.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Event-free survival (EFS)</measure>
      <time_frame>24 mouths</time_frame>
      <description>EFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, start of new anti-cancer treatment, relapse, death of any cause or discontinued due to any adverse events.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>24 mouths</time_frame>
      <description>OS is defined as the time from the signing of informed consent form to the date of the last survival follow-up or death due to any cause.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>In vivo cellular Pharmacokinetic (PK) profile of HY004.</measure>
      <time_frame>24 mouths</time_frame>
      <description>To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in blood by quantitative polymerase chain reaction(qPCR) and Flow Cytometry.</description>
    </other_outcome>
    <other_outcome>
      <measure>In vivo cellular pharmacodynamics (PD) profile of HY004.</measure>
      <time_frame>3 mouths</time_frame>
      <description>To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum.</description>
    </other_outcome>
    <other_outcome>
      <measure>Prevalence and incidence of humoral immunogenicity to HY004.</measure>
      <time_frame>24 mouths</time_frame>
      <description>To characterize the concentration of anti-drug antibodies</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Non-hodgkin Lymphoma</condition>
    <arm_group>
      <arm_group_label>Single dose of HY004</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients received a single dose of anti-CD22/CD19 CAR T cells after receiving a conditioning regimen of cyclophosphamide and fludarabine.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>HY004</intervention_name>
      <description>Autologous 2nd generation bispecific CAR-T cells targeting both CD22 and CD19, single infusion intravenously.&#xD;
  Start Dose level: 2.00 x 10^6/kg CAR+T-cells</description>
      <arm_group_label>Single dose of HY004</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            1. Patients who are willing to sign the informed consent form;&#xD;
  &#xD;
            2. Aged 18-75 years, male or female;&#xD;
  &#xD;
            3. Previously received≥2nd-line adequate therapy or hematopoietic stem cell&#xD;
               transplantation (HSCT), and patients with CD19+/CD22+ relapsed/refractory B-NHL&#xD;
               according to the WHO classification 2017, which are provided specifically as follows:&#xD;
  &#xD;
                 1. Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS);&#xD;
  &#xD;
                 2. Primary mediastinal large B cell lymphoma (PMBCL);&#xD;
  &#xD;
                 3. Grade 3b follicular lymphoma;&#xD;
  &#xD;
                 4. Transformed follicular lymphoma;&#xD;
  &#xD;
                 5. High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high&#xD;
                    grade B cell lymphoma - not otherwise specified.&#xD;
  &#xD;
            4. Measurable imaging lesion at screening: Intranodal lesion must have a long diameter of&#xD;
               more than 1.5 cm, and extranodal lesion must have a long diameter of more than 1.0 cm&#xD;
               with PET-positive disease by Lugano classification .&#xD;
  &#xD;
            5. PET-positive disease BY Lugano classification&#xD;
  &#xD;
            6. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function.&#xD;
  &#xD;
            7. Adequate vascular access for leukapheresis procedure&#xD;
  &#xD;
            8. Subjects who have received previous CD19-targeted therapy must have CD19-positive&#xD;
               lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            1. Active Central Nervous System (CNS) involvement by malignancy.&#xD;
  &#xD;
            2. Patients with existing central nervous system disease or with a history of central&#xD;
               nervous system disease.&#xD;
  &#xD;
            3. Patients receiving any of the following drugs or therapies within the specified period&#xD;
               prior to apheresis:&#xD;
  &#xD;
                 1. Alemtuzumab and Bendamustine within 6 months prior to apheresis;&#xD;
  &#xD;
                 2. Cladribine within 3 months prior to apheresis;&#xD;
  &#xD;
                 3. Lenalidomide within 1 mouth prior to apheresis;&#xD;
  &#xD;
                 4. Lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than&#xD;
                    3 half-lives prior to apheresis is eligible;&#xD;
  &#xD;
                 5. Anti-CD20 monoclonal antibody and therapeutic dose of hormones within 7 d prior&#xD;
                    to apheresis;&#xD;
  &#xD;
                 6. Non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than&#xD;
                    3 half-lives prior to apheresis is eligible;&#xD;
  &#xD;
                 7. Venetoclax (BCL-2 inhibitor) within 4 d prior to apheresis;&#xD;
  &#xD;
                 8. Idelalisib (PI3Kδ kinase inhibitor) within 2 d prior to apheresis;&#xD;
  &#xD;
                 9. DLI within 6 weeks prior to apheresis;&#xD;
  &#xD;
                10. Radiotherapy within 6 weeks prior to apheresis - progressive disease at&#xD;
                    radiotherapy site, or PET positive lesion at other non-radiotherapy site is&#xD;
                    eligible;&#xD;
  &#xD;
            4. Patients previously received CAR-T cell therapy, the products that have same&#xD;
               indication and have beenlisted in China are eligible;&#xD;
  &#xD;
            5. Patients who have previously received allogeneic hematopoietic stem cell&#xD;
               transplantation (allo-HSCT) within 3 mouths.&#xD;
  &#xD;
            6. Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD&#xD;
               within 4 weeks before screening.&#xD;
  &#xD;
            7. Active systemic autoimmune disease.&#xD;
  &#xD;
            8. Known infection with human immunodeficiency virus (HIV) or chronic infection with&#xD;
               hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive).&#xD;
  &#xD;
            9. Patients with active infections at screening.&#xD;
  &#xD;
           10. History of cardiovascular disease.&#xD;
  &#xD;
           11. Pregnant or nursing women.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Junyin Yu</last_name>
      <phone>+86 010-65960098</phone>
      <email>yujunyin@juventas.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HY004</keyword>
    <keyword>CD22/CD19 Chimeric Antigen Receptor T-cells</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>
      <mesh_term>Lymphoma, B-Cell</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/NCT06005649
  org study id: HY004102
  nct id: NCT06005649
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a multi-center, open-label, single-arm, phase I/II trial to evaluate the safety and
        efficacy of HY004 treatment in Adult patients with relapsed or refractory B-cell
        Non-Hodgkin's Lymphoma (r/r B-NHL).
  This trial is a multi-center, open label, single-arm, phase I/II trial to evaluate the safety
        and efficacy of HY004 in Adult(aged 18~75 years old) patients with r/r B-NHL.
  
        The phase I part of the trial is to evaluate the safety, optimal dose of HY004,
        Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Adult
        patients with r/r B-NHL. The phase II part of the trial is to evaluate the efficacy and
        safety of HY004 in in the treatment of Adult patients with r/r B-NHL. The study includes
        screening, pre-treatment (Cell Product manufacture & lymphodepletion), HY004 infusion ,
        safety and efficacy follow-up, and survival follow-up. All subjects who have received HY004
        infusion will be followed for up to 2 years.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 【Phase I】Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)
  time frame: 28 days
  description: Determine the MTD and DLT of HY004 in the Treatment and recommend the dose for Phase II study.
  measure: 【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
  time frame: 3 months
  description: Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.
  measure: 【Phase I】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
  time frame: 3 months
  description: Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.
  measure: Safety of CNCT19 therapy: CTCAE v5.0
  time frame: 24 months
  description: Safety measures include adverse events as assessed by CTCAE v5.0.
  measure: Complete Remission Rate (CRR)
  time frame: 3 months
  description: Efficacy of HY004 as measured by CR at 3 months after HY004 Cell Injection infusion.
  measure: ORR（CR+PR）/CRR
  time frame: 28 days
  description: Efficacy of HY004 as measured by ORR/CRR at 28 days after cell infusion.
  measure: ORR（CR+PR）/CRR
  time frame: 6 months
  description: Efficacy of HY004 as measured by ORR/CRR at 6 months after cell infusion.
  measure: Best Overall Response (BOR)
  time frame: 24 mouths
  description: The best overall response after HY004 infusion.
  measure: Duration of Remission (DOR)
  time frame: 24 mouths
  description: DOR means the duration from reaching the response (e.g., CR or PR) criteria of the therapy to the first, clearly defined progressive disease, or death for disease under investigation.
  measure: Progression-free survival (PFS)
  time frame: 24 mouths
  description: PFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, or death for any reason.
  measure: Event-free survival (EFS)
  time frame: 24 mouths
  description: EFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, start of new anti-cancer treatment, relapse, death of any cause or discontinued due to any adverse events.
  measure: Overall survival (OS)
  time frame: 24 mouths
  description: OS is defined as the time from the signing of informed consent form to the date of the last survival follow-up or death due to any cause.
  measure: In vivo cellular Pharmacokinetic (PK) profile of HY004.
  time frame: 24 mouths
  description: To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in blood by quantitative polymerase chain reaction(qPCR) and Flow Cytometry.
  measure: In vivo cellular pharmacodynamics (PD) profile of HY004.
  time frame: 3 mouths
  description: To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum.
  measure: Prevalence and incidence of humoral immunogenicity to HY004.
  time frame: 24 mouths
  description: To characterize the concentration of anti-drug antibodies
  arm group label: Single dose of HY004
  arm group type: Experimental
  description: Patients received a single dose of anti-CD22/CD19 CAR T cells after receiving a conditioning regimen of cyclophosphamide and fludarabine.
  intervention type: Biological
  intervention name: HY004
  description: Autologous 2nd generation bispecific CAR-T cells targeting both CD22 and CD19, single infusion intravenously.
  Start Dose level: 2.00 x 10^6/kg CAR+T-cells
  arm group label: Single dose of HY004
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Junyin Yu
  phone: +86 010-65960098
  email: yujunyin@juventas.cn
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, Non-Hodgkin
  mesh term: Lymphoma, B-Cell
  sharing ipd: No