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/NCT06039436</url>
    </required_header>
    <id_info>
      <org_study_id>CBSAA001</org_study_id>
      <nct_id>NCT06039436</nct_id>
    </id_info>
    <brief_title>Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired SAA Receiving sUCBT</brief_title>
    <official_title>Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired Severe Aplastic Aplasia Receiving Single Cord Blood Transplant: A Multi-center, Single-arm Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Anhui Provincial Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Anhui Provincial Hospital</source>
    <oversight_info>
      <has_dmc>No</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>
        To evaluate the safety and efficacy of Single Umbilical Cord blood transplantation (sUCBT)&#xD;
        containing low dose ATG based conditioning regimen in the treatment of acquired Severe&#xD;
        Aplastic Anemia (SAA).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hematopoietic stem cell transplantation (HSCT) from HLA-compatible sibling donors is the&#xD;
        standard preferred therapy for Severe Aplastic Anemia (SAA). At present, HLA-compatible&#xD;
        donors in China fail to meet the needs of patients for transplantation. Umbilical Cord blood&#xD;
        transplantation (UCBT) is an alternative treatment for patients with emergency conditions who&#xD;
        lack compatible sibling donors, have failed immunosuppressant therapies or cannot wait for&#xD;
        unrelated fully compatible donors. However, implantation failure is one of the main problems&#xD;
        in UCBT for SAA due to the low cord blood stem cells. Nowadays, there is no consensus on the&#xD;
        optimal conditioning regimen for UCBT treatment of SAA, and whether ATG should be added to&#xD;
        the conditioning regimen is still controversial. Early clinical studies in UCBT have shown&#xD;
        that the sufficient ATG in the conditioning regimen will lead to a decrease rate of&#xD;
        implantation rate and affect survival of UCBT ultimately. However, a range of recent studies&#xD;
        have found that with the addition of low-dose ATG, T cell reconstitution seems to outperform&#xD;
        bone marrow or peripheral blood stem cell transplantation. Therefore, how to properly use ATG&#xD;
        to both retain its effective GVHD prevention effect and reduce its impact on immune&#xD;
        reconstruction has important clinical significance for improving the transplantation&#xD;
        efficacy. In this study, a multicenter clinical study will be conducted to observe the safety&#xD;
        and efficacy of UCBT with low dose ATG in the treatment of SAA and the long-term quality of&#xD;
        life of patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">May 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2025</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>12 Months</target_duration>
    <primary_outcome>
      <measure>The one-year probability of GRFS</measure>
      <time_frame>one year</time_frame>
      <description>GRFS is defined as survival without grade III-IV acute GVHD immunosuppression requiring chronic GVHD or relapse.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The cumulative incidence of platelet engraftment at 28 days after transplantation</measure>
      <time_frame>28 days</time_frame>
      <description>Platelet engraftment is defined as independent from platelet transfusion for at least 7 days with a platelet count of more than 20 × 10^9/L.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The cumulative incidence of neutrophil engraftment at 28 days after transplantation</measure>
      <time_frame>28 days</time_frame>
      <description>Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of platelet engraftment</measure>
      <time_frame>28 days</time_frame>
      <description>Platelet engraftment is defined as independent from platelet transfusion for at least 7 days with a platelet count of more than 20 × 10^9/L.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of neutrophil engraftment</measure>
      <time_frame>28 days</time_frame>
      <description>Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The cumulative incidence of acute GVHD at 100 days after transplantation</measure>
      <time_frame>100 days</time_frame>
      <description>Acute GVHD is defined that occurs within 100 days after transplantation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The cumulative incidence of chronic GVHD at 100 days after transplantation</measure>
      <time_frame>one year</time_frame>
      <description>Chronic GVHD is defined that occurs 100 days after transplantation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immune reconstitution after transplantation</measure>
      <time_frame>one year</time_frame>
      <description>The level of immunoglobulin, T cells, B cells and NK cells reconstitution after transplantation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The 180-day probability of TRM</measure>
      <time_frame>180 days</time_frame>
      <description>TRM(transplant-related mortality) is defined that death due to any transplant-related cause within 180 days after transplantation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The incidence of infection</measure>
      <time_frame>one year</time_frame>
      <description>Infection is defined as various post-transplant associated infections</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The one-year probability of OS</measure>
      <time_frame>one year</time_frame>
      <description>OS (overall survival) is defined as the time which begins at diagnosis and up to the time of death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The one-year probability of DFS</measure>
      <time_frame>one year</time_frame>
      <description>DFS (disease free survival) is defined as the time from treatment until the recurrence of disease (or death) after transplantation</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">72</enrollment>
    <condition>Severe Aplastic Anemia</condition>
    <arm_group>
      <arm_group_label>ATG group</arm_group_label>
      <description>Patients in the ATG group will be treated with conditioning regimen containing ATG 2mg/kg on day -7 prior to transplant.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Anti-Thymocyte Globulin (Rabbit)</intervention_name>
      <description>Indications for trial stopping: subjects occur pregnancy events, severe organ function impairments, or emergency events related or unrelated to treatment; or subjects are unwilling to continue participating in the clinical trial.</description>
      <arm_group_label>ATG group</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          patients with indications for hematopoietic stem cell transplantation and initially&#xD;
          diagnosed with severe aplastic anemia or have not responded to immunosuppressive therapy&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients diagnosed with severe aplastic anemia who do not respond to initial diagnosis&#xD;
               or immunosuppressive therapy;&#xD;
  &#xD;
            -  Patients meet diagnostic criteria for severe aplastic anemia (Camitta criteria);&#xD;
  &#xD;
            -  Age from 1 to 50 years old, male or female;&#xD;
  &#xD;
            -  Patients without HLA-matched sibling or unrelated donors avaliable;&#xD;
  &#xD;
            -  Patients who have undergone unrelated cord blood transplantation need to have HLA&#xD;
               high-resolution matching、TNC (before cord blood freezing)≥3.0×107/kg、CD34+(before cord&#xD;
               blood freezing)≥1.5×107/kg、tubule recovery rate≥80%;&#xD;
  &#xD;
            -  patients and their family members or guardians agreed to the study and signed informed&#xD;
               consent;&#xD;
  &#xD;
            -  No severe organ failure;&#xD;
  &#xD;
            -  ECOG score≤2 and HCT-CI≤2;&#xD;
  &#xD;
            -  serum ferritin (SF)&lt;1000ug/L;&#xD;
  &#xD;
            -  women of reproductive agemust have a negative pregnancy test and agree to use&#xD;
               effective contraception during treatment and for one year thereafter.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  patients with inherited bone marrow failure syndromes;&#xD;
  &#xD;
            -  Positive for HLA-A, B, Cw, DRB1, DQB1, DPB1 site-specific HLA antibodies for donor&#xD;
               cord blood with solid-phase fluorescence assay;&#xD;
  &#xD;
            -  patients who have previously received allogeneic hematopoietic stem cell&#xD;
               transplantation or solid organ transplantation;&#xD;
  &#xD;
            -  Uncontrolled bacterial, viral, or fungal infections;&#xD;
  &#xD;
            -  HIV infection or active viral hepatitis B or C infection;&#xD;
  &#xD;
            -  Pregnant or breastfeeding women;&#xD;
  &#xD;
            -  patients with a history of primary malignancy within 3 years prior to transplant&#xD;
               treatment;&#xD;
  &#xD;
            -  patients receiving ATG treatment within 2 weeks before transplantation;&#xD;
  &#xD;
            -  patients with drug dependent or uncontrolled mental illness or cognitive impairment;&#xD;
  &#xD;
            -  Participants in other similar clinical studies within 3 months;&#xD;
  &#xD;
            -  Patients allergic to ATG;&#xD;
  &#xD;
            -  patients considered unsuitable for inclusion by the researchers.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Year</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Xiaoyu Zhu, ph.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>The First Affiliated Hospital of University of Science and Technology of China (Anhui Provicial Hospital)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xiaoyu Zhu, ph.D</last_name>
      <phone>15255456091</phone>
      <email>xiaoyuz@ustc.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Baolin Tang, M.D</last_name>
      <phone>13856901277</phone>
      <email>zwcrystalbl@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)</name>
        <address>
          <city>Hefei</city>
          <state>Anhui</state>
          <zip>230036</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Xiaoyu Zhu, ph.D</last_name>
        <phone>15255456091</phone>
        <email>xiaoyuz@ustc.cn</email>
      </contact>
      <contact_backup>
        <last_name>Baolin Tang, M.D</last_name>
        <phone>13856901277</phone>
        <email>zwcrystalbl@163.com</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 9, 2023</last_update_submitted>
    <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Anhui Provincial Hospital</investigator_affiliation>
      <investigator_full_name>Xiaoyu Zhu</investigator_full_name>
      <investigator_title>Chief physician</investigator_title>
    </responsible_party>
    <keyword>Anti-Thymocyte Globulin (Rabbit)</keyword>
    <keyword>Umbilical Cord Blood Transplantation</keyword>
    <keyword>Severe Aplastic Anemia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anemia, Aplastic</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Antilymphocyte Serum</mesh_term>
      <mesh_term>Thymoglobulin</mesh_term>
    </intervention_browse>
    <!-- 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/NCT06039436
  org study id: CBSAA001
  nct id: NCT06039436
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  To evaluate the safety and efficacy of Single Umbilical Cord blood transplantation (sUCBT)
        containing low dose ATG based conditioning regimen in the treatment of acquired Severe
        Aplastic Anemia (SAA).
  Hematopoietic stem cell transplantation (HSCT) from HLA-compatible sibling donors is the
        standard preferred therapy for Severe Aplastic Anemia (SAA). At present, HLA-compatible
        donors in China fail to meet the needs of patients for transplantation. Umbilical Cord blood
        transplantation (UCBT) is an alternative treatment for patients with emergency conditions who
        lack compatible sibling donors, have failed immunosuppressant therapies or cannot wait for
        unrelated fully compatible donors. However, implantation failure is one of the main problems
        in UCBT for SAA due to the low cord blood stem cells. Nowadays, there is no consensus on the
        optimal conditioning regimen for UCBT treatment of SAA, and whether ATG should be added to
        the conditioning regimen is still controversial. Early clinical studies in UCBT have shown
        that the sufficient ATG in the conditioning regimen will lead to a decrease rate of
        implantation rate and affect survival of UCBT ultimately. However, a range of recent studies
        have found that with the addition of low-dose ATG, T cell reconstitution seems to outperform
        bone marrow or peripheral blood stem cell transplantation. Therefore, how to properly use ATG
        to both retain its effective GVHD prevention effect and reduce its impact on immune
        reconstruction has important clinical significance for improving the transplantation
        efficacy. In this study, a multicenter clinical study will be conducted to observe the safety
        and efficacy of UCBT with low dose ATG in the treatment of SAA and the long-term quality of
        life of patients.
  observational model: Cohort
  time perspective: Prospective
  measure: The one-year probability of GRFS
  time frame: one year
  description: GRFS is defined as survival without grade III-IV acute GVHD immunosuppression requiring chronic GVHD or relapse.
  measure: The cumulative incidence of platelet engraftment at 28 days after transplantation
  time frame: 28 days
  description: Platelet engraftment is defined as independent from platelet transfusion for at least 7 days with a platelet count of more than 20 × 10^9/L.
  measure: The cumulative incidence of neutrophil engraftment at 28 days after transplantation
  time frame: 28 days
  description: Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.
  measure: Time of platelet engraftment
  time frame: 28 days
  description: Platelet engraftment is defined as independent from platelet transfusion for at least 7 days with a platelet count of more than 20 × 10^9/L.
  measure: Time of neutrophil engraftment
  time frame: 28 days
  description: Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.
  measure: The cumulative incidence of acute GVHD at 100 days after transplantation
  time frame: 100 days
  description: Acute GVHD is defined that occurs within 100 days after transplantation
  measure: The cumulative incidence of chronic GVHD at 100 days after transplantation
  time frame: one year
  description: Chronic GVHD is defined that occurs 100 days after transplantation
  measure: Immune reconstitution after transplantation
  time frame: one year
  description: The level of immunoglobulin, T cells, B cells and NK cells reconstitution after transplantation
  measure: The 180-day probability of TRM
  time frame: 180 days
  description: TRM(transplant-related mortality) is defined that death due to any transplant-related cause within 180 days after transplantation
  measure: The incidence of infection
  time frame: one year
  description: Infection is defined as various post-transplant associated infections
  measure: The one-year probability of OS
  time frame: one year
  description: OS (overall survival) is defined as the time which begins at diagnosis and up to the time of death
  measure: The one-year probability of DFS
  time frame: one year
  description: DFS (disease free survival) is defined as the time from treatment until the recurrence of disease (or death) after transplantation
  arm group label: ATG group
  description: Patients in the ATG group will be treated with conditioning regimen containing ATG 2mg/kg on day -7 prior to transplant.
  intervention type: Drug
  intervention name: Anti-Thymocyte Globulin (Rabbit)
  description: Indications for trial stopping: subjects occur pregnancy events, severe organ function impairments, or emergency events related or unrelated to treatment; or subjects are unwilling to continue participating in the clinical trial.
  arm group label: ATG group
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Year
  maximum age: 50 Years
  healthy volunteers: No
  last name: Xiaoyu Zhu, ph.D
  role: Principal Investigator
  affiliation: The First Affiliated Hospital of University of Science and Technology of China (Anhui Provicial Hospital)
  last name: Xiaoyu Zhu, ph.D
  phone: 15255456091
  email: xiaoyuz@ustc.edu.cn
  last name: Baolin Tang, M.D
  phone: 13856901277
  email: zwcrystalbl@163.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Anhui Provincial Hospital
  investigator full name: Xiaoyu Zhu
  investigator title: Chief physician
  mesh term: Anemia, Aplastic
  mesh term: Antilymphocyte Serum
  mesh term: Thymoglobulin