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/NCT06009107</url>
    </required_header>
    <id_info>
      <org_study_id>HY004101</org_study_id>
      <nct_id>NCT06009107</nct_id>
    </id_info>
    <brief_title>A Study of HY004 Treatment in Adult Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)</brief_title>
    <acronym>B-ALL</acronym>
    <official_title>A Phase I/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of HY004 in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)</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, phase I/II trial to evaluate the safety and efficacy of HY004&#xD;
        treatment in Adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia&#xD;
        (r/r B-cell ALL).&#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 treatment in Adult (aged 18~65 years old) patients with r/r B-cell ALL.&#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-cell ALL. 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-cell ALL. The study includes&#xD;
        screening, pre-treatment (Cell Product manufacture &amp; lymphodepletion), HY004 infusion, safety&#xD;
        and efficacy follow-up, and survival follow-up. All subjects who have received HY004 infusion&#xD;
        will be followed for up to 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 18, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 30, 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>Overall Remission Rate (ORR)</measure>
      <time_frame>at the end of Month 3</time_frame>
      <description>ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Remission Rate (ORR)</measure>
      <time_frame>within 3 months</time_frame>
      <description>ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Best overall response (BOR)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity</measure>
      <time_frame>at the end of Month 3</time_frame>
      <description>Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators; MRD negativity as determined using flow cytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of remission (DOR)</measure>
      <time_frame>to data cutoff date</time_frame>
      <description>DOR is defined as the time between their first complete response per independent review to relapse or any death in the absence of documented relapse.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Allogeneic Stem Cell Transplant (Allo-SCT) rate</measure>
      <time_frame>First infusion date of HY004 to data cutoff date(up to 2 years)</time_frame>
      <description>The proportion of patients who have received Allo-SCT after HY004 treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relapse Free Survival (RFS)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>RFS is defined as the time from the HY004 infusion date to the date of disease relapse or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Event-Free Survival(EFS)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>EFS is defined as the time from the HY004 infusion date to the date of any event, including disease progression, cessation of treatment for any reason, or death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>2 years</time_frame>
      <description>OS is defined as the time from the HY004 Cell Injection infusion to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to HY004.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of transgene copy number per genomic DNA (gDNA) amount.</measure>
      <time_frame>Up to 3 months(BM sample); Up to 2 years(Blood sample)</time_frame>
      <description>To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by quantitative polymerase chain reaction(qPCR).</description>
    </other_outcome>
    <other_outcome>
      <measure>In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of percent of CAR-positive cells.</measure>
      <time_frame>Up to 3 months(BM sample); Up to 2 years(Blood sample)</time_frame>
      <description>To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by Flow Cytometry.</description>
    </other_outcome>
    <other_outcome>
      <measure>In vivo cellular pharmacodynamics (PD) profile of HY004.</measure>
      <time_frame>28 days</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>2 years</time_frame>
      <description>To characterize the concentration of anti-drug antibodies.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>B-cell Acute Lymphoblastic Leukemia</condition>
    <arm_group>
      <arm_group_label>Participant Group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>HY004</intervention_name>
      <description>A single infusion of Autologous 2nd generation CD19/CD22-directed CAR-T cells administered intravenously.</description>
      <arm_group_label>Participant Group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>Administered intravenously.</description>
      <arm_group_label>Participant Group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine Phosphate</intervention_name>
      <description>Administered intravenously.</description>
      <arm_group_label>Participant Group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signed written informed consent prior to any study procedures (patient and/or parent&#xD;
               or legal guardian);&#xD;
  &#xD;
            2. Gender is not limited, and the age at the time of screening is ≥ 18 years old and ≤ 65&#xD;
               years old;&#xD;
  &#xD;
            3. Relapsed or refractory acute lymphoblastic leukemia (ALL);&#xD;
  &#xD;
            4. Documentation of CD19 and/orCD22 tumor expression demonstrated in bone marrow or&#xD;
               peripheral blood within 3 months before screening;&#xD;
  &#xD;
            5. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening;&#xD;
  &#xD;
            6. ECOG score 0-1 points;&#xD;
  &#xD;
            7. Organ function requirements: All patients must have adequate renal and liver&#xD;
               functions.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Active Central Nervous System (CNS) involvement by malignancy;&#xD;
  &#xD;
            2. Isolated extra-medullary disease relapse;&#xD;
  &#xD;
            3. Patients with Burkitt's lymphoma/leukemia;&#xD;
  &#xD;
            4. History of concomitant genetic syndrome;&#xD;
  &#xD;
            5. Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD&#xD;
               within 4 weeks before screening; Patients with a history of allogeneic hematopoietic&#xD;
               stem cell transplantation within 12 weeks before single collection;&#xD;
  &#xD;
            6. Active systemic autoimmune disease;&#xD;
  &#xD;
            7. 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;
            8. Patients with active infections at screening;&#xD;
  &#xD;
            9. Patients who have used CAR-T cell therapy before screening;&#xD;
  &#xD;
           10. Patients with an expected lifespan of less than 3 months.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jianxiang Wang M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Study Principal Investigator Institute of Hematology &amp; Blood Diseases Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>JunYin Yu PM</last_name>
      <phone>+86-010-65960098</phone>
      <email>yujunyin@juventas.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HY004</keyword>
    <keyword>Cluster of differentiation antigen 19 and/or 22(CD19 and/or 22)</keyword>
    <keyword>CD19/22-directed CAR-T cells</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
      <mesh_term>Leukemia, Lymphoid</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Fludarabine phosphate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Currently the investigators have no plan of interim anaylsis, the investigators don't plan to share individual participant data(IPD) during the trial on-going.</ipd_description>
    </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/NCT06009107
  org study id: HY004101
  nct id: NCT06009107
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a multi-center, phase I/II trial to evaluate the safety and efficacy of HY004
        treatment in Adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia
        (r/r B-cell ALL).
  This trial is a multi-center, open label, single-arm, phase I/II trial to evaluate the safety
        and efficacy of HY004 treatment in Adult (aged 18~65 years old) patients with r/r B-cell ALL.
  
        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-cell ALL. 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-cell ALL. 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: Overall Remission Rate (ORR)
  time frame: at the end of Month 3
  description: ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC).
  measure: Overall Remission Rate (ORR)
  time frame: within 3 months
  description: ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification.
  measure: Best overall response (BOR)
  time frame: up to 2 years
  description: The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.
  measure: Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity
  time frame: at the end of Month 3
  description: Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators; MRD negativity as determined using flow cytometry.
  measure: Duration of remission (DOR)
  time frame: to data cutoff date
  description: DOR is defined as the time between their first complete response per independent review to relapse or any death in the absence of documented relapse.
  measure: Allogeneic Stem Cell Transplant (Allo-SCT) rate
  time frame: First infusion date of HY004 to data cutoff date(up to 2 years)
  description: The proportion of patients who have received Allo-SCT after HY004 treatment.
  measure: Relapse Free Survival (RFS)
  time frame: up to 2 years
  description: RFS is defined as the time from the HY004 infusion date to the date of disease relapse or death from any cause.
  measure: Event-Free Survival(EFS)
  time frame: up to 2 years
  description: EFS is defined as the time from the HY004 infusion date to the date of any event, including disease progression, cessation of treatment for any reason, or death.
  measure: Overall survival (OS)
  time frame: 2 years
  description: OS is defined as the time from the HY004 Cell Injection infusion to the date of death from any cause.
  measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）
  time frame: up to 2 years
  description: Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to HY004.
  measure: In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of transgene copy number per genomic DNA (gDNA) amount.
  time frame: Up to 3 months(BM sample); Up to 2 years(Blood sample)
  description: To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by quantitative polymerase chain reaction(qPCR).
  measure: In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of percent of CAR-positive cells.
  time frame: Up to 3 months(BM sample); Up to 2 years(Blood sample)
  description: To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by Flow Cytometry.
  measure: In vivo cellular pharmacodynamics (PD) profile of HY004.
  time frame: 28 days
  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: 2 years
  description: To characterize the concentration of anti-drug antibodies.
  arm group label: Participant Group
  arm group type: Experimental
  description: Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
  intervention type: Biological
  intervention name: HY004
  description: A single infusion of Autologous 2nd generation CD19/CD22-directed CAR-T cells administered intravenously.
  arm group label: Participant Group
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: Administered intravenously.
  arm group label: Participant Group
  intervention type: Drug
  intervention name: Fludarabine Phosphate
  description: Administered intravenously.
  arm group label: Participant Group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Jianxiang Wang M.D.
  role: Principal Investigator
  affiliation: Study Principal Investigator Institute of Hematology & Blood Diseases Hospital
  last name: JunYin Yu PM
  phone: +86-010-65960098
  email: yujunyin@juventas.cn
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Leukemia, Lymphoid
  mesh term: Cyclophosphamide
  mesh term: Fludarabine
  mesh term: Fludarabine phosphate
  sharing ipd: No
  ipd description: Currently the investigators have no plan of interim anaylsis, the investigators don't plan to share individual participant data(IPD) during the trial on-going.