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/NCT05996393</url>
    </required_header>
    <id_info>
      <org_study_id>AVA-3</org_study_id>
      <nct_id>NCT05996393</nct_id>
    </id_info>
    <brief_title>CsA+ATG+AVA vs. CsA+AVA for the Treatment of Newly-diagnosed SAA in the Elderly</brief_title>
    <official_title>Ciclosporin + Antithymocyte Immunoglobulin + Avatrombpag Versus Ciclosporin + Avatrombpag for the Treatment of 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>
      <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>
        This is a multicenter, prospective, randonmized study. Our previous retrospective study&#xD;
        showed that for SAA patients who were intolerant to ATG, CsA+ eltrombopag (EPAG) had similar&#xD;
        efficacy to CsA+ATG+EPAG. Since the action mechanism of AVA and EPAG is not exactly the same,&#xD;
        and the metabolic level of the elderly is not the same as that of younger patients, it is&#xD;
        unknown whether there are predictive factors of efficacy in the treatment of AVA. We wondered&#xD;
        whether CsA+AVA could achieve an efficacy similar to CsA+ATG+AVA in the Elderly. Meanwhile,&#xD;
        to explore the predictive factors of efficacy, to find out a safe and effective treatment&#xD;
        strategy for the Elderly.&#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. For SAA patients with o condition of hematopoietic stem cell&#xD;
        transplantation, guideline recommended ciclosporin A (CsA) + anti-thymocyte immunoglobulin&#xD;
        (ATG) + thrombopoietin receptor agonists (TPO-RA) as the first-line therapy. Our previous&#xD;
        retrospective study showed that for SAA patients who were intolerant to ATG, CsA+ eltrombopag&#xD;
        (EPAG) had similar efficacy to CsA+ATG+EPAG. However, the adverse effects such as&#xD;
        hepatotoxicity and gasrointestinal disorder limit its application in elderly SAA.Compared&#xD;
        with EPAG, AVA has no hepatotoxicity and less other adverse effects, but there was few&#xD;
        studies for AA. Our previous study demonstrated that AVA was effective in 55% of refractory&#xD;
        AA. Since the action mechanism of AVA and EPAG is not exactly the same, and the metabolic&#xD;
        level of the elderly is not the same as that of younger patients, it is unknown whether there&#xD;
        are predictive factors of efficacy in the treatment of AVA. Thus, we wondered whether CsA+AVA&#xD;
        could achieve an efficacy similar to CsA+ATG+AVA in the Elderly.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2026</completion_date>
    <primary_completion_date type="Anticipated">October 2025</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Overall response rate</measure>
      <time_frame>6 month</time_frame>
      <description>Proportion of patient who achieved partial response or complete response</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Complete response rate</measure>
      <time_frame>6 month</time_frame>
      <description>Proportion of patient who achieved complete response (HGB&gt;100g/L, PLT&gt;100×109/L, ANC&gt;1.0×109/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relapse rate</measure>
      <time_frame>12 month</time_frame>
      <description>Proportion of patient who relapse</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse event rate</measure>
      <time_frame>3, 6, 12 month</time_frame>
      <description>Proportion of patient who adverse events</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Aplastic Anemia</condition>
    <arm_group>
      <arm_group_label>CsA+ATG+AVA</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Ciclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Anti-human thymocyte: rabbit anti-human thymocyte globulin (r-ATG 3mg/kg/d) was administered intravenously for 5 days; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CsA+AVA</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Ciclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ciclosporin</intervention_name>
      <description>3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml</description>
      <arm_group_label>CsA+ATG+AVA</arm_group_label>
      <arm_group_label>CsA+AVA</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Avatrombopag</intervention_name>
      <description>60 mg/d orally, 24 weeks</description>
      <arm_group_label>CsA+ATG+AVA</arm_group_label>
      <arm_group_label>CsA+AVA</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Anti-Human Thymocyte Immunoglobulin, Rabbit</intervention_name>
      <description>rabbit anti-human thymocyte immunoglobulin (r-ATG 3mg/kg/d), intravenously, 5 days;</description>
      <arm_group_label>CsA+ATG+AVA</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients with newly diagnosed severe aplastic anemia, aged greater than 60 years.&#xD;
  &#xD;
            2. Patients met the diagnostic criteria of severe aplastic anemia (SAA).&#xD;
  &#xD;
            3. Complete all screening assessments as outlined in the test protocol.&#xD;
  &#xD;
            4. Without or with no more than 1 month treatment of ciclosporine, tacrolimus,&#xD;
               glucocortocoid, or TPO-RAs.&#xD;
  &#xD;
            5. Agree to sign the informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia)&#xD;
               and other causes of cytopenia.&#xD;
  &#xD;
            2. Patients with uncontrolled bleeding and/or infection despite standard treatment.&#xD;
  &#xD;
            3. Patients with previous history of hematopoietic stem cell transplantation.&#xD;
  &#xD;
            4. Patients with previous history of thrombosis in 1 year.&#xD;
  &#xD;
            5. Patients with concurrent malignancy.&#xD;
  &#xD;
            6. Those who are considered unsuitable for enrollment by the investigator.&#xD;
  &#xD;
            7. Abnormal renal function: creatinine &gt; 1.2 normal upper limit, albumin &lt; 0.9 normal&#xD;
               lower limit, or CLcr &lt; 30 ml/min.&#xD;
  &#xD;
            8. Abnormal liver function: transaminase &gt; 2.5 normal upper limit, or tota bilirubin &gt;&#xD;
               2.5 normal upper limit.&#xD;
  &#xD;
            9. Patients with severe heart, liver or renal disease.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>60 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Bing Han, Doctor</last_name>
      <phone>+86-010-69155760</phone>
      <email>hanbing_li@sina.com.cn</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>
    <reference>
      <citation>Yang Y, Tang Z, Huang Y, Hu Q, Wang S, Ji J, Du Y, Yang C, Chen M, Hu S, Han B. Sirolimus versus cyclosporine A in patients with primary acquired pure red cell aplasia: a prospective cohort study. Blood Cancer J. 2023 May 10;13(1):74. doi: 10.1038/s41408-023-00845-3. No abstract available.</citation>
      <PMID>37160872</PMID>
    </reference>
    <reference>
      <citation>Chi Y, Hu Q, Yang C, Chen M, Han B. Avatrombopag is effective in patients with chemoradiotherapy-induced aplastic anemia: a single-center, retrospective study. Exp Hematol. 2023 Jan;117:62-68. doi: 10.1016/j.exphem.2022.11.002. Epub 2022 Nov 16.</citation>
      <PMID>36400314</PMID>
    </reference>
    <reference>
      <citation>Wan Z, Chen M, Han B. Avatrombopag, a promising novel thrombopoietin receptor agonist for refractory/relapsed/intolerant non-severe aplastic anemia: a phase 2 single-arm clinical trial. Ann Med. 2023 Dec;55(1):2224044. doi: 10.1080/07853890.2023.2224044.</citation>
      <PMID>37318085</PMID>
    </reference>
    <reference>
      <citation>Chen F, Hu S, Ruan J, Chen M, Han B. Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria. Blood Cancer J. 2021 Mar 16;11(3):58. doi: 10.1038/s41408-021-00451-1. No abstract available. Erratum In: Blood Cancer J. 2021 May 6;11(5):85.</citation>
      <PMID>33727526</PMID>
    </reference>
    <reference>
      <citation>Chen M, Liu Q, Gao Y, Suo X, Ding X, Wang L, Li L, Shao Y, Gao D, Sun W, Tan Y, Wang W, Ye F, Han B. Cyclosporine plus eltrombopag in the treatment of aplastic anemia with or without antithymocyte immunoglobulin: A multicenter real-world retrospective study. Eur J Haematol. 2023 Sep;111(3):407-413. doi: 10.1111/ejh.14021. Epub 2023 Jun 4.</citation>
      <PMID>37271577</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 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 18, 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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cyclosporine</mesh_term>
      <mesh_term>Cyclosporins</mesh_term>
      <mesh_term>Thymoglobulin</mesh_term>
      <mesh_term>Immunoglobulins</mesh_term>
      <mesh_term>Immunoglobulins, Intravenous</mesh_term>
      <mesh_term>Antibodies</mesh_term>
    </intervention_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/NCT05996393
  org study id: AVA-3
  nct id: NCT05996393
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, prospective, randonmized study. Our previous retrospective study
        showed that for SAA patients who were intolerant to ATG, CsA+ eltrombopag (EPAG) had similar
        efficacy to CsA+ATG+EPAG. Since the action mechanism of AVA and EPAG is not exactly the same,
        and the metabolic level of the elderly is not the same as that of younger patients, it is
        unknown whether there are predictive factors of efficacy in the treatment of AVA. We wondered
        whether CsA+AVA could achieve an efficacy similar to CsA+ATG+AVA in the Elderly. Meanwhile,
        to explore the predictive factors of efficacy, to find out a safe and effective treatment
        strategy for the Elderly.
  Aplastic anemia (AA) can be divided into severe AA (SAA) and non-severe AA (NSAA), according
        to the severity of the disease. For SAA patients with o condition of hematopoietic stem cell
        transplantation, guideline recommended ciclosporin A (CsA) + anti-thymocyte immunoglobulin
        (ATG) + thrombopoietin receptor agonists (TPO-RA) as the first-line therapy. Our previous
        retrospective study showed that for SAA patients who were intolerant to ATG, CsA+ eltrombopag
        (EPAG) had similar efficacy to CsA+ATG+EPAG. However, the adverse effects such as
        hepatotoxicity and gasrointestinal disorder limit its application in elderly SAA.Compared
        with EPAG, AVA has no hepatotoxicity and less other adverse effects, but there was few
        studies for AA. Our previous study demonstrated that AVA was effective in 55% of refractory
        AA. Since the action mechanism of AVA and EPAG is not exactly the same, and the metabolic
        level of the elderly is not the same as that of younger patients, it is unknown whether there
        are predictive factors of efficacy in the treatment of AVA. Thus, we wondered whether CsA+AVA
        could achieve an efficacy similar to CsA+ATG+AVA in the Elderly.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall response rate
  time frame: 6 month
  description: Proportion of patient who achieved partial response or complete response
  measure: Complete response rate
  time frame: 6 month
  description: Proportion of patient who achieved complete response (HGB>100g/L, PLT>100×109/L, ANC>1.0×109/L)
  measure: Relapse rate
  time frame: 12 month
  description: Proportion of patient who relapse
  measure: Adverse event rate
  time frame: 3, 6, 12 month
  description: Proportion of patient who adverse events
  arm group label: CsA+ATG+AVA
  arm group type: Experimental
  description: Ciclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Anti-human thymocyte: rabbit anti-human thymocyte globulin (r-ATG 3mg/kg/d) was administered intravenously for 5 days; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
  arm group label: CsA+AVA
  arm group type: Experimental
  description: Ciclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
  intervention type: Drug
  intervention name: Ciclosporin
  description: 3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml
  arm group label: CsA+ATG+AVA
  arm group label: CsA+AVA
  intervention type: Drug
  intervention name: Avatrombopag
  description: 60 mg/d orally, 24 weeks
  arm group label: CsA+ATG+AVA
  arm group label: CsA+AVA
  intervention type: Drug
  intervention name: Anti-Human Thymocyte Immunoglobulin, Rabbit
  description: rabbit anti-human thymocyte immunoglobulin (r-ATG 3mg/kg/d), intravenously, 5 days;
  arm group label: CsA+ATG+AVA
  criteria: 
  gender: All
  minimum age: 60 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Bing Han, Doctor
  phone: +86-010-69155760
  email: hanbing_li@sina.com.cn
  facility: 
  country: China
  citation: Yang Y, Tang Z, Huang Y, Hu Q, Wang S, Ji J, Du Y, Yang C, Chen M, Hu S, Han B. Sirolimus versus cyclosporine A in patients with primary acquired pure red cell aplasia: a prospective cohort study. Blood Cancer J. 2023 May 10;13(1):74. doi: 10.1038/s41408-023-00845-3. No abstract available.
  PMID: 37160872
  citation: Chi Y, Hu Q, Yang C, Chen M, Han B. Avatrombopag is effective in patients with chemoradiotherapy-induced aplastic anemia: a single-center, retrospective study. Exp Hematol. 2023 Jan;117:62-68. doi: 10.1016/j.exphem.2022.11.002. Epub 2022 Nov 16.
  PMID: 36400314
  citation: Wan Z, Chen M, Han B. Avatrombopag, a promising novel thrombopoietin receptor agonist for refractory/relapsed/intolerant non-severe aplastic anemia: a phase 2 single-arm clinical trial. Ann Med. 2023 Dec;55(1):2224044. doi: 10.1080/07853890.2023.2224044.
  PMID: 37318085
  citation: Chen F, Hu S, Ruan J, Chen M, Han B. Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria. Blood Cancer J. 2021 Mar 16;11(3):58. doi: 10.1038/s41408-021-00451-1. No abstract available. Erratum In: Blood Cancer J. 2021 May 6;11(5):85.
  PMID: 33727526
  citation: Chen M, Liu Q, Gao Y, Suo X, Ding X, Wang L, Li L, Shao Y, Gao D, Sun W, Tan Y, Wang W, Ye F, Han B. Cyclosporine plus eltrombopag in the treatment of aplastic anemia with or without antithymocyte immunoglobulin: A multicenter real-world retrospective study. Eur J Haematol. 2023 Sep;111(3):407-413. doi: 10.1111/ejh.14021. Epub 2023 Jun 4.
  PMID: 37271577
  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
  mesh term: Cyclosporine
  mesh term: Cyclosporins
  mesh term: Thymoglobulin
  mesh term: Immunoglobulins
  mesh term: Immunoglobulins, Intravenous
  mesh term: Antibodies
  sharing ipd: No