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/NCT06004752</url>
    </required_header>
    <id_info>
      <org_study_id>Avatrombopag-2</org_study_id>
      <nct_id>NCT06004752</nct_id>
    </id_info>
    <brief_title>A Single-center, Single-arm, Prospective Clinical Study on the Efficacy and Safety of CsA+AVA in the Treatment of NSAA in the Elderly</brief_title>
    <official_title>A Single-center, Single-arm, Prospective Clinical Study on the Efficacy and Safety of Cyclosporine Combined With Avatrombopag in the Treatment of Non-severe Aplastic Anemia in the Elderly</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking Union Medical College Hospital</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>
        For elderly patients who cannot tolerate anti-thymocyte globulin (ATG) treatment, the&#xD;
        addition of avatrombopag (AVA), which has a slight adverse reaction, can theoretically&#xD;
        improve the hematological response rate in elderly patients with non-severe aplastic anemia&#xD;
        (NSAA) without significantly increasing adverse reactions. Based on this, this study treated&#xD;
        NSAA patients older than 60 with AVA combined with CsA to evaluate the hematological response&#xD;
        rate and safety of AVA in the elderly who could not tolerate ATG therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Aplastic anemia (AA) can be divided into severe AA (SAA) and non-severe AA (NSAA), according&#xD;
        to the severity of the disease. Anti-thymocyte globulin (ATG) in combination with CsA is the&#xD;
        most typical combined immunosuppressive therapy regimen. For elderly patients who cannot&#xD;
        tolerate anti-thymocyte globulin (ATG) treatment, the addition of avatrombopag, which has a&#xD;
        slight adverse reaction, can theoretically improve the hematological response rate in elderly&#xD;
        patients with NSAA without significantly increasing adverse reactions. Based on this, this&#xD;
        study treated NSAA patients older than 60 with AVA combined with CsA to evaluate the&#xD;
        hematological response rate and safety of AVA in the elderly who could not tolerate ATG&#xD;
        therapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
    <phase>Phase 4</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>ORR at 6 Months</measure>
      <time_frame>6 months</time_frame>
      <description>Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion</measure>
      <time_frame>6 months</time_frame>
      <description>The change in hematology values ( haemoglobin) were evaluated</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in Platelet in the Absence of Platelet Transfusion</measure>
      <time_frame>6 months</time_frame>
      <description>The change in hematology values (platelet) were evaluated</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia</measure>
      <time_frame>12 months</time_frame>
      <description>Clonal evolution to myelodysplasia is defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Evolution to leukemia is defined as greater than 20% peripheral blood and/or marrow blasts. Evolution to paroxysmal nocturnal hemoglobinuria (PNH) is defined as a clone at baseline &lt; 10% that rose to greater than 50% on study.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Aplastic Anemia</condition>
    <arm_group>
      <arm_group_label>treatment group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cyclosporine: 3mg/kg/d orally divided into two times, the valley concentration of cyclosporine maintained at 100~150ng/ml, to achieve the maximum effect and began to reduce after 3 months, the reduction of 25mg every 3 months;&#xD;
  Avatrombopag: The dosage was 40~60mg orally, once a day, and the dosage was adjusted according to the subject's platelet count. The drug was administered for 24 weeks (6 months).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Avatrombopag+CsA</intervention_name>
      <description>Cyclosporine was taken orally at 3mg/kg/d twice, and the valley concentration of cyclosporine was maintained at 100-150ng /ml.&#xD;
  Avatrombopag：The dosage is 40~60mg, once a day, orally.(If the patient has a hematological reaction and platelets rapidly rise to PLT&gt;200×10^9/L, the drug should be stopped and observed until the PLT&lt;100×109/L and then reduced by one titration dose; If the platelet recovered to 100-200 ×10^9/L for more than 2 months, the titration dose was reduced by one. After the reduction to 20mg, platelets can still be maintained at 100~200×10^9/L, and for more than 2 months, the reduction to 20mg 1/ every other day; After the reduction, platelets can still be maintained at 100-200 ×10^9/L for more than 2 months</description>
      <arm_group_label>treatment group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Elderly patients with well-defined NSAA anemia who meet the diagnostic criteria for&#xD;
               aplastic anemia (AA) but do not meet the diagnostic criteria for severe aplastic&#xD;
               anemia (SAA). AA is diagnosed if at least two of the following conditions are met:&#xD;
               hemoglobin &lt;100 g/L, platelet count &lt;50×109/L, and neutrophil count &lt;1.5×10^9/L. SAA&#xD;
               diagnostic criteria: Meet the following diagnostic criteria, at least two of the&#xD;
               following three criteria meet PLT &lt; 20×10^9/L, ANC &lt; 0.5×10^9/L, ARC &lt; 60×10^9/L or&#xD;
               red blood cell corrected volume &lt;1%.&#xD;
  &#xD;
            2. Age 65 years or older, male or female.&#xD;
  &#xD;
            3. Subjects must complete all screening assessments listed in the trial protocol.&#xD;
  &#xD;
            4. Able to swallow or administer orally.&#xD;
  &#xD;
            5. Cannot tolerate or refuse ATG treatment.&#xD;
  &#xD;
            6. No previous treatment with cyclosporine, tacrolimus or hormones or treatment for less&#xD;
               than 1 month.&#xD;
  &#xD;
            7. No TPO receptor agonists (including thrombopoietin, aitripopar, tritripopar, etc.)&#xD;
               were used or TPO receptor agonists were used to treat the total dose of&#xD;
               thrombopoietin, Eltrombopag, Herombopag, Avatrombopag and other TPO receptor agonists&#xD;
               ≤1 week.&#xD;
  &#xD;
            8. Informed consent must be signed before the start of all specific research procedures.&#xD;
               Considering the patient's condition, if the patient's signature is not conducive to&#xD;
               the treatment of the disease, the informed consent shall be signed by the patient's&#xD;
               immediate family.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known congenital hematopoietic exhaustion diseases (such as Fanconi anemia) and other&#xD;
               causes of pancytopenia and bone marrow hypoproliferative diseases (such as hemolytic&#xD;
               PNH, hypoproliferative MDS/AML, autoantibody-mediated pancytopenia, etc.);&#xD;
  &#xD;
            2. Patients with uncontrolled bleeding and/or infection after standard treatment.&#xD;
  &#xD;
            3. Patients with a history of hematopoietic stem cell transplantation.&#xD;
  &#xD;
            4. History of high blood pressure.&#xD;
  &#xD;
            5. History of thrombosis.&#xD;
  &#xD;
            6. Patients with underlying cancer who also have malignant tumors or are receiving&#xD;
               immunosuppressive therapy.&#xD;
  &#xD;
            7. Participants considered unsuitable for inclusion by the researchers.&#xD;
  &#xD;
            8. Renal function indicators: serum creatinine &gt;1.2 times the upper limit of normal (ULN)&#xD;
               or albumin &lt;0.9 times the lower limit of normal (LLN); Patients with severe renal&#xD;
               insufficiency with creatinine clearance &lt;30ml/min;&#xD;
  &#xD;
            9. Liver function indicators: alanine aminotransferase (ALT) is 2.5 times higher than the&#xD;
               upper limit of normal or AST is 2.5 times higher than the upper limit of normal or&#xD;
               total bilirubin is 2.5 times higher than the upper limit of normal or serum creatinine&#xD;
               is 1.5 times higher than the upper limit of normal;&#xD;
  &#xD;
           10. Serious heart, liver and kidney disease.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>65 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Bing Han</last_name>
      <phone>+861069151235</phone>
      <email>hanbing_li@sina.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Peking union medical college hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
      <investigator_full_name>Bing Han</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anemia</mesh_term>
      <mesh_term>Anemia, Aplastic</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>individual participant data would be accepted upon request</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>always</ipd_time_frame>
      <ipd_access_criteria>email request</ipd_access_criteria>
    </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/NCT06004752
  org study id: Avatrombopag-2
  nct id: NCT06004752
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  For elderly patients who cannot tolerate anti-thymocyte globulin (ATG) treatment, the
        addition of avatrombopag (AVA), which has a slight adverse reaction, can theoretically
        improve the hematological response rate in elderly patients with non-severe aplastic anemia
        (NSAA) without significantly increasing adverse reactions. Based on this, this study treated
        NSAA patients older than 60 with AVA combined with CsA to evaluate the hematological response
        rate and safety of AVA in the elderly who could not tolerate ATG therapy.
  Aplastic anemia (AA) can be divided into severe AA (SAA) and non-severe AA (NSAA), according
        to the severity of the disease. Anti-thymocyte globulin (ATG) in combination with CsA is the
        most typical combined immunosuppressive therapy regimen. For elderly patients who cannot
        tolerate anti-thymocyte globulin (ATG) treatment, the addition of avatrombopag, which has a
        slight adverse reaction, can theoretically improve the hematological response rate in elderly
        patients with NSAA without significantly increasing adverse reactions. Based on this, this
        study treated NSAA patients older than 60 with AVA combined with CsA to evaluate the
        hematological response rate and safety of AVA in the elderly who could not tolerate ATG
        therapy.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: ORR at 6 Months
  time frame: 6 months
  description: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26
  measure: Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion
  time frame: 6 months
  description: The change in hematology values ( haemoglobin) were evaluated
  measure: Changes in Platelet in the Absence of Platelet Transfusion
  time frame: 6 months
  description: The change in hematology values (platelet) were evaluated
  measure: Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia
  time frame: 12 months
  description: Clonal evolution to myelodysplasia is defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Evolution to leukemia is defined as greater than 20% peripheral blood and/or marrow blasts. Evolution to paroxysmal nocturnal hemoglobinuria (PNH) is defined as a clone at baseline < 10% that rose to greater than 50% on study.
  arm group label: treatment group
  arm group type: Experimental
  description: Cyclosporine: 3mg/kg/d orally divided into two times, the valley concentration of cyclosporine maintained at 100~150ng/ml, to achieve the maximum effect and began to reduce after 3 months, the reduction of 25mg every 3 months;
  Avatrombopag: The dosage was 40~60mg orally, once a day, and the dosage was adjusted according to the subject's platelet count. The drug was administered for 24 weeks (6 months).
  intervention type: Drug
  intervention name: Avatrombopag+CsA
  description: Cyclosporine was taken orally at 3mg/kg/d twice, and the valley concentration of cyclosporine was maintained at 100-150ng /ml.
  Avatrombopag：The dosage is 40~60mg, once a day, orally.(If the patient has a hematological reaction and platelets rapidly rise to PLT>200×10^9/L, the drug should be stopped and observed until the PLT<100×109/L and then reduced by one titration dose; If the platelet recovered to 100-200 ×10^9/L for more than 2 months, the titration dose was reduced by one. After the reduction to 20mg, platelets can still be maintained at 100~200×10^9/L, and for more than 2 months, the reduction to 20mg 1/ every other day; After the reduction, platelets can still be maintained at 100-200 ×10^9/L for more than 2 months
  arm group label: treatment group
  criteria: 
  gender: All
  minimum age: 65 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Bing Han
  phone: +861069151235
  email: hanbing_li@sina.com
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Peking Union Medical College Hospital
  investigator full name: Bing Han
  investigator title: Professor
  mesh term: Anemia
  mesh term: Anemia, Aplastic
  sharing ipd: Yes
  ipd description: individual participant data would be accepted upon request
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: always
  ipd access criteria: email request