<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/NCT02203396</url>
  </required_header>
  <id_info>
    <org_study_id>ATGIIT201401</org_study_id>
    <nct_id>NCT02203396</nct_id>
  </id_info>
  <brief_title>A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia</brief_title>
  <acronym>OSP</acronym>
  <official_title>A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yizhou Zheng</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Hematology &amp; Blood Diseases Hospital, China</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Severe acquired aplastic anaemia (SAA) is a bone marrow failure disease characterized by&#xD;
      pancytopenia and a hypocellular bone marrow. The corn pathophysiological mechanism is the&#xD;
      destruction of hematopoietic stem/progenitor cells mediated by auto-reactive effector T&#xD;
      cells. Immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine&#xD;
      (CSA) is currently the standard of treatment in patients with aplastic anaemia who are not&#xD;
      eligible for bone marrow transplantation and with response rates from 40% to 70%. Previous&#xD;
      studies showed that horse ATG (hATG) is apparently more effective than rabbit ATG (rATG) as&#xD;
      the latter has higher treatment related mortality (TRM). Unfortunately hATG is unavailable in&#xD;
      China, so we conduct a optimized standard treatment (9 days protocol) of rATG plus CSA and&#xD;
      Levamisole (LMS) Sequential maintaining (termed Optimized Standard Protocol, OSP) for severe&#xD;
      aplastic anemia. This prospective study is designed to evaluate the efficacy and safety of&#xD;
      Optimized Standard Protocol as first line therapy in newly diagnosed severe aplastic anemia&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During the treatment period, rATG is administered at a dose of 1.97 mg/kg/day for 9 days by&#xD;
      slow intravenous infusion. CSA is administered orally at a dose of 3 mg/kg qod, and&#xD;
      Levamisole was administered orally at a dose of 2.5 mg/kg qod. The CSA and Levamisole (LMS)&#xD;
      is designed to alternately every other day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">September 2017</completion_date>
  <primary_completion_date type="Anticipated">September 2016</primary_completion_date>
  <phase>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>the response and complete remission rate with Optimized Standard Protocol.</measure>
    <time_frame>month +6</time_frame>
    <description>Response will be evaluated at each clinic visit. Complete response (CR) was defined as achieving all three peripheral blood count criteria: (1) Hb level up to the normal range; (2) ANC≥1.5×109/L; (3) PLT≥100×109/L.&#xD;
Partial response (PR) was defined as transfusion independent, no longer meeting criteria for severe disease. Persistence of transfusion requirement or death was evidence of no response (NR).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.</measure>
    <time_frame>month +12, month +60</time_frame>
    <description>Relapse was defined as a responder who met criteria for SAA again after achieving response and keeping stable blood counts for at least 3 months.&#xD;
Sustained response (SR) was defined as Hb &gt; 10 g/dL at month +12 and +60, in the absence of any treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Aplastic Anemia</condition>
  <arm_group>
    <arm_group_label>Severe Aplastic Anemia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: rabbit ATG, Cyclosporine, Levamisole</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rabbit ATG, Cyclosporine, Levamisole</intervention_name>
    <description>rATG is administered at a dose of 1.97 mg/kg/day for 9 days CSA is administered orally at a dose of 3 mg/kg qod Levamisole is administered orally at a dose of 2.5 mg/kg qod. The CSA and LMS is designed to alternately every other day.</description>
    <arm_group_label>Severe Aplastic Anemia</arm_group_label>
    <other_name>rATG</other_name>
    <other_name>CSA</other_name>
    <other_name>LMS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed SAA (according to the standard criteria)&#xD;
&#xD;
               1. Bone marrow cellularity less than 30% (excluding lymphocytes)&#xD;
&#xD;
               2. At least two of the following: Absolute neutrophil count less than 500/ uL;&#xD;
                  Platelet count less than 20,000/ uL; Absolute reticulocyte count less than&#xD;
                  20,000/ uL.&#xD;
&#xD;
          -  Age greater than or equal to 6 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Serum creatinine greater than 2.5 mg/dL&#xD;
&#xD;
          -  Underlying carcinoma (except local cervical, basal cell, squamous cell)&#xD;
&#xD;
          -  Prior immunosuppressive therapy with ATG, antilymphocyte globulin (ALG), or high dose&#xD;
             cyclophosphamide.&#xD;
&#xD;
          -  Current pregnancy or lactation or unwillingness to take oral contraceptives or use an&#xD;
             effective method of birth control.&#xD;
&#xD;
          -  Diagnosis of Fanconi anemia or other congenital bone marrow failure syndromes&#xD;
&#xD;
          -  Evidence of a clonal disorder on cytogenetics. Patients with super severe neutropenia&#xD;
             (ANC less than 200/uL) will not be excluded if results of cytogenetics are not&#xD;
             available or pending.&#xD;
&#xD;
          -  Underlying immunodeficiency state including seropositivity for HIV&#xD;
&#xD;
          -  Inability to understand the investigational nature of the study or give informed&#xD;
             consent&#xD;
&#xD;
          -  Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary,&#xD;
             infectious, or metabolic disease of such severity that it would preclude the patient s&#xD;
             ability to tolerate protocol therapy, or that death within 7-10 days is likely.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zheng Yizhou, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nie Neng</last_name>
    <email>docnn@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>TianJin</city>
        <state>Tianjin</state>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nie Neng</last_name>
      <phone>+86 22 23909023</phone>
      <email>docnn@163.com</email>
    </contact>
    <investigator>
      <last_name>Zheng Yizhou, M.D., Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003 Mar 5;289(9):1130-5. doi: 10.1001/jama.289.9.1130.</citation>
    <PMID>12622583</PMID>
  </results_reference>
  <results_reference>
    <citation>Camitta BM, Rappeport JM, Parkman R, Nathan DG. Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood. 1975 Mar;45(3):355-63.</citation>
    <PMID>1090310</PMID>
  </results_reference>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>July 27, 2014</study_first_submitted>
  <study_first_submitted_qc>July 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>May 3, 2016</last_update_submitted>
  <last_update_submitted_qc>May 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</investigator_affiliation>
    <investigator_full_name>Yizhou Zheng</investigator_full_name>
    <investigator_title>Yizhou Zheng, Vice director Institute of Hematology &amp; Blood Diseases Hospital</investigator_title>
  </responsible_party>
  <keyword>SAA</keyword>
  <keyword>Immunosuppressive treatment</keyword>
  <keyword>ATG</keyword>
  <keyword>Cyclosporine</keyword>
  <keyword>Levamisole</keyword>
  <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>Levamisole</mesh_term>
    <mesh_term>Cyclosporins</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02203396
org study id: ATGIIT201401
nct id: NCT02203396
lead sponsor: 
has dmc: Yes
Severe acquired aplastic anaemia (SAA) is a bone marrow failure disease characterized by
      pancytopenia and a hypocellular bone marrow. The corn pathophysiological mechanism is the
      destruction of hematopoietic stem/progenitor cells mediated by auto-reactive effector T
      cells. Immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine
      (CSA) is currently the standard of treatment in patients with aplastic anaemia who are not
      eligible for bone marrow transplantation and with response rates from 40% to 70%. Previous
      studies showed that horse ATG (hATG) is apparently more effective than rabbit ATG (rATG) as
      the latter has higher treatment related mortality (TRM). Unfortunately hATG is unavailable in
      China, so we conduct a optimized standard treatment (9 days protocol) of rATG plus CSA and
      Levamisole (LMS) Sequential maintaining (termed Optimized Standard Protocol, OSP) for severe
      aplastic anemia. This prospective study is designed to evaluate the efficacy and safety of
      Optimized Standard Protocol as first line therapy in newly diagnosed severe aplastic anemia
      patients.
During the treatment period, rATG is administered at a dose of 1.97 mg/kg/day for 9 days by
      slow intravenous infusion. CSA is administered orally at a dose of 3 mg/kg qod, and
      Levamisole was administered orally at a dose of 2.5 mg/kg qod. The CSA and Levamisole (LMS)
      is designed to alternately every other day.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the response and complete remission rate with Optimized Standard Protocol.
time frame: month +6
description: Response will be evaluated at each clinic visit. Complete response (CR) was defined as achieving all three peripheral blood count criteria: (1) Hb level up to the normal range; (2) ANC≥1.5×109/L; (3) PLT≥100×109/L.
Partial response (PR) was defined as transfusion independent, no longer meeting criteria for severe disease. Persistence of transfusion requirement or death was evidence of no response (NR).
measure: Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.
time frame: month +12, month +60
description: Relapse was defined as a responder who met criteria for SAA again after achieving response and keeping stable blood counts for at least 3 months.
Sustained response (SR) was defined as Hb > 10 g/dL at month +12 and +60, in the absence of any treatment.
arm group label: Severe Aplastic Anemia
arm group type: Experimental
description: Drug: rabbit ATG, Cyclosporine, Levamisole
intervention type: Drug
intervention name: rabbit ATG, Cyclosporine, Levamisole
description: rATG is administered at a dose of 1.97 mg/kg/day for 9 days CSA is administered orally at a dose of 3 mg/kg qod Levamisole is administered orally at a dose of 2.5 mg/kg qod. The CSA and LMS is designed to alternately every other day.
arm group label: Severe Aplastic Anemia
other name: rATG
other name: CSA
other name: LMS
criteria: 
gender: All
minimum age: 6 Years
maximum age: 70 Years
healthy volunteers: No
last name: Zheng Yizhou, M.D., Ph.D
role: Principal Investigator
affiliation: Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
last name: Nie Neng
email: docnn@163.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003 Mar 5;289(9):1130-5. doi: 10.1001/jama.289.9.1130.
PMID: 12622583
citation: Camitta BM, Rappeport JM, Parkman R, Nathan DG. Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood. 1975 Mar;45(3):355-63.
PMID: 1090310
responsible party type: Sponsor-Investigator
investigator affiliation: Institute of Hematology & Blood Diseases Hospital, China
investigator full name: Yizhou Zheng
investigator title: Yizhou Zheng, Vice director Institute of Hematology & Blood Diseases Hospital
mesh term: Anemia
mesh term: Anemia, Aplastic
mesh term: Cyclosporine
mesh term: Levamisole
mesh term: Cyclosporins
mesh term: Thymoglobulin