<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/NCT04403321</url>
  </required_header>
  <id_info>
    <org_study_id>ELT-1</org_study_id>
    <nct_id>NCT04403321</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients</brief_title>
  <official_title>Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients</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>
      This is a randomized, open-label, phase II study to compare the efficacy of eltrombopag&#xD;
      combined with tacrolimus to eltrombopag alone in Chinese subjects with refractory or relapsed&#xD;
      aplastic anemia. The safety would also be evaluated. Patients would be randomized to receive&#xD;
      eltrombopag alone or eltrombopag combined with tacrolimus. Treatment with eltrombopag will be&#xD;
      started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count&#xD;
      up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with&#xD;
      the target trough concentration of 4-10 ng/mL throughout the study. The hematological&#xD;
      response rate and safety will be recorded and compared at 3, 6 months and 1 year after&#xD;
      starting the study treatment (Week 13, 26 and 52).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">July 31, 2022</completion_date>
  <primary_completion_date type="Actual">July 30, 2022</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ORR at 6 Months</measure>
    <time_frame>Week 26</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>ORR at 3 Months</measure>
    <time_frame>Week 14</time_frame>
    <description>ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion</measure>
    <time_frame>Week 26</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>Week 26</time_frame>
    <description>The change in hematology values (platelet) were evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hematologic response</measure>
    <time_frame>by 6 months (all patients), at 24 months (responders only)</time_frame>
    <description>Time from the date of the start of the first response to the date of first relapse defined as again meeting criteria for aplastic anemia</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>2</number_of_arms>
  <enrollment type="Actual">114</enrollment>
  <condition>Aplastic Anemia</condition>
  <condition>Drug Effect</condition>
  <arm_group>
    <arm_group_label>Eltrombopag</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Eltrombopag and the placebo would be applied. Eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Eltrombopag + Tacrolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eltrombopag and tacrolimus would be applied. Eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with the target trough concentration of 4-10 ng/mL throughout the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Tacrolimus will be given at 1mg bid with the target trough concentration to be 4-10 ng/mL.</description>
    <arm_group_label>Eltrombopag + Tacrolimus</arm_group_label>
    <other_name>experimental</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for Tacrolimus)</intervention_name>
    <description>placebo will be given at 1mg bid.</description>
    <arm_group_label>Eltrombopag</arm_group_label>
    <other_name>control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient with a previous diagnosis of aplastic anemia and had no response or relapsed&#xD;
             following at least one treatment course in a period time of ≥ 6 months of&#xD;
             immunosuppression containing CsA or CsA+anti-thymocyte globulin (ATG);&#xD;
&#xD;
          2. Current diagnosis of aplastic anemia by bone marrow biopsy;&#xD;
&#xD;
          3. did not receive HSCT nor were HSCT candidates;&#xD;
&#xD;
          4. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2;&#xD;
&#xD;
          5. Patient with QTcF (Fridericia's QT correction formula) at screening &lt;450 msec, or &lt;480&#xD;
             msec with bundle branch block, as determined via the mean of a triplicate ECG and&#xD;
             assessed at site.&#xD;
&#xD;
          6. Subjects are able to understand and comply with protocol requirements and instructions&#xD;
             and have signed and dated informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Congenital aplastic anemia;&#xD;
&#xD;
          2. Presence of chromosomal aberration;&#xD;
&#xD;
          3. Evidence of a clonal hematologic bone marrow disorder on cytogenetics;&#xD;
&#xD;
          4. Have any concomitant malignancies and must be fully recovered from treatment for any&#xD;
             other malignancy and have been disease-free for 5 years;&#xD;
&#xD;
          5. AST or ALT ≥3 times the upper limit of normal;&#xD;
&#xD;
          6. Serum creatinine, total bilirubin, or alkaline phosphatase &gt;1.5 x ULN;&#xD;
&#xD;
          7. Cardiac disorder (NYHA) functional classification Grade II/III/IV;&#xD;
&#xD;
          8. Past history of thromboembolic event (including anti-phospholipid antibody syndrome)&#xD;
             and current use of anticoagulants;&#xD;
&#xD;
          9. Infection not adequately responding to appropriate therapy;&#xD;
&#xD;
         10. Other known or suspected underlying primary immunodeficiency;&#xD;
&#xD;
         11. Prior treatment with eltrombopag, romiplostim, or any other TPO (thrombopoietin)&#xD;
             receptor agonist;&#xD;
&#xD;
         12. Pregnant or nursing (lactating) woman;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <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>January 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 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>Tacrolimus</mesh_term>
  </intervention_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_time_frame>10 years</ipd_time_frame>
    <ipd_access_criteria>email request</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04403321
org study id: ELT-1
nct id: NCT04403321
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a randomized, open-label, phase II study to compare the efficacy of eltrombopag
      combined with tacrolimus to eltrombopag alone in Chinese subjects with refractory or relapsed
      aplastic anemia. The safety would also be evaluated. Patients would be randomized to receive
      eltrombopag alone or eltrombopag combined with tacrolimus. Treatment with eltrombopag will be
      started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count
      up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with
      the target trough concentration of 4-10 ng/mL throughout the study. The hematological
      response rate and safety will be recorded and compared at 3, 6 months and 1 year after
      starting the study treatment (Week 13, 26 and 52).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ORR at 6 Months
time frame: Week 26
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: ORR at 3 Months
time frame: Week 14
description: ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence.
measure: Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion
time frame: Week 26
description: The change in hematology values ( haemoglobin) were evaluated
measure: Changes in Platelet in the Absence of Platelet Transfusion
time frame: Week 26
description: The change in hematology values (platelet) were evaluated
measure: Duration of hematologic response
time frame: by 6 months (all patients), at 24 months (responders only)
description: Time from the date of the start of the first response to the date of first relapse defined as again meeting criteria for aplastic anemia
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: Eltrombopag
arm group type: Placebo Comparator
description: Eltrombopag and the placebo would be applied. Eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved.
arm group label: Eltrombopag + Tacrolimus
arm group type: Experimental
description: Eltrombopag and tacrolimus would be applied. Eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with the target trough concentration of 4-10 ng/mL throughout the study.
intervention type: Drug
intervention name: Tacrolimus
description: Tacrolimus will be given at 1mg bid with the target trough concentration to be 4-10 ng/mL.
arm group label: Eltrombopag + Tacrolimus
other name: experimental
intervention type: Drug
intervention name: Placebo (for Tacrolimus)
description: placebo will be given at 1mg bid.
arm group label: Eltrombopag
other name: control
criteria: 
gender: All
minimum age: 14 Years
maximum age: 85 Years
healthy volunteers: No
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
mesh term: Tacrolimus
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 time frame: 10 years
ipd access criteria: email request