<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/NCT02241018</url>
  </required_header>
  <id_info>
    <org_study_id>NFH-MSC-aGVHD-2014</org_study_id>
    <nct_id>NCT02241018</nct_id>
  </id_info>
  <brief_title>MSCs Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant aGVHD</brief_title>
  <official_title>Mesenchymal Stem Cells Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guangdong Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Third Affiliated Hospital, Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangzhou General Hospital of Guangzhou Military Command</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangzhou First People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Southern Medical University, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Huazhong University of Science and Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academy Military Medical Science, China</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Nanfang Hospital, Southern Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy of CD25 monoclonal antibody and&#xD;
      calcineurin inhibitors with or without mesenchymal stem cells (MSCs) in treating patients&#xD;
      with steroid-resistant acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic&#xD;
      stem cell transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for&#xD;
      several hematological disorders. Although good progress has been made in the prevention and&#xD;
      treatment of side effects associated with transplantation, aGVHDremains a common and&#xD;
      life-threatening complication with poor prognosis. Corticosteroids are still acted as the&#xD;
      first-line treatments of aGVHD, with a response rate of 50-80. However, those who failed to&#xD;
      initial therapy only have 10-30% long-term survival.&#xD;
&#xD;
      Mesenchymal stromal cells (MSCs) are a form of multipotent adult stem cells that can be&#xD;
      isolated from many tissues, such as bone marrow (BM), adipose tissue and umbilical cord. Such&#xD;
      cells possess the capacity to suppress immunological responses, support hematopoiesis and&#xD;
      repair tissues. Clinical applications of human MSCs are evolving rapidly for preventing and&#xD;
      treating GVHD. Although the results are still controversy, most prospective and retrospective&#xD;
      data suggest that MSCs are effective to aGVHD.&#xD;
&#xD;
      In the present study, the investigators will prospectively evaluate the efficacy and safety&#xD;
      of ex-vivo-expanded BM-derived MSCs from third-party donors combined with CD25 monoclonal&#xD;
      antibody and calcineurin inhibitors in treating patients with aGVHD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">September 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</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>The efficacy of treatment for steroid-resistant aGVHD</measure>
    <time_frame>1 year</time_frame>
    <description>The responses to aGVHD are according to the literature criteria, including completely response (CR), partial response (PR) and no response (NR), and CR is defined as resolution of all symptoms of aGVHD; PR is defined as a decrease by at least 1 GVHD stage in any 1 organ system without deterioration in others 24. Overall response (OR) includes CR and PR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of infections</measure>
    <time_frame>1 year</time_frame>
    <description>Infections are mainly focused on cytomegalovirus (CMV) and Epstein-Barr virus ( EBV) infections during study treatments and within one year after study treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of primary underlying disease relapse</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of chronic GVHD</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Acute Graft-versus-host Disease</condition>
  <arm_group>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MSCs will be given at a median dose of 1×10^6 cells/kg once weekly for 4 dose (as 1 cycle) or until CR. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. Besides, CD25 monoclonal antibody (20mg/kg) will be administered at day 1,4,8,15, 21 and calcineurin inhibitors will also be used.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CD25 Mc Ab &amp; calcineurin inhibitors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CD25 monoclonal antibody (20mg/kg, day 1,4,8,15,21) will be administered combined with calcineurin inhibitors. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CD25 monoclonal antibody</intervention_name>
    <arm_group_label>CD25 Mc Ab &amp; calcineurin inhibitors</arm_group_label>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>calcineurin inhibitors</intervention_name>
    <arm_group_label>CD25 Mc Ab &amp; calcineurin inhibitors</arm_group_label>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MSCs</intervention_name>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age of 14-65 years&#xD;
&#xD;
          -  steroid-resistant aGVHD&#xD;
&#xD;
          -  subjects (or their legally acceptable representatives) must have signed an informed&#xD;
             consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood&#xD;
             pressure)&#xD;
&#xD;
          -  Patients with any conditions not suitable for the trial (investigators' decision)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qifa Liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nanfang Hospital, Southern Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ren Lin</last_name>
    <phone>+86-020-62787883</phone>
    <email>lansinglinren@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Hematology,Nanfang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ren Lin, MD</last_name>
      <phone>+86-020-62787883</phone>
      <email>lansinglinren@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Qifa Liu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.</citation>
    <PMID>15121408</PMID>
  </reference>
  <reference>
    <citation>Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Diez Campelo M, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011 Jul;96(7):1072-6. doi: 10.3324/haematol.2010.038356. Epub 2011 Mar 10.</citation>
    <PMID>21393326</PMID>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 13, 2014</study_first_submitted>
  <study_first_submitted_qc>September 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>September 13, 2014</last_update_submitted>
  <last_update_submitted_qc>September 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanfang Hospital, Southern Medical University</investigator_affiliation>
    <investigator_full_name>Qifa Liu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Hematopoietic Stem Cell Transplantation</keyword>
  <keyword>Mesenchymal Stem Cells</keyword>
  <keyword>CD25 Monoclonal Antibody</keyword>
  <keyword>Acute Graft-versus-host disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Calcineurin Inhibitors</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/NCT02241018
org study id: NFH-MSC-aGVHD-2014
nct id: NCT02241018
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to compare the efficacy of CD25 monoclonal antibody and
      calcineurin inhibitors with or without mesenchymal stem cells (MSCs) in treating patients
      with steroid-resistant acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic
      stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for
      several hematological disorders. Although good progress has been made in the prevention and
      treatment of side effects associated with transplantation, aGVHDremains a common and
      life-threatening complication with poor prognosis. Corticosteroids are still acted as the
      first-line treatments of aGVHD, with a response rate of 50-80. However, those who failed to
      initial therapy only have 10-30% long-term survival.

      Mesenchymal stromal cells (MSCs) are a form of multipotent adult stem cells that can be
      isolated from many tissues, such as bone marrow (BM), adipose tissue and umbilical cord. Such
      cells possess the capacity to suppress immunological responses, support hematopoiesis and
      repair tissues. Clinical applications of human MSCs are evolving rapidly for preventing and
      treating GVHD. Although the results are still controversy, most prospective and retrospective
      data suggest that MSCs are effective to aGVHD.

      In the present study, the investigators will prospectively evaluate the efficacy and safety
      of ex-vivo-expanded BM-derived MSCs from third-party donors combined with CD25 monoclonal
      antibody and calcineurin inhibitors in treating patients with aGVHD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The efficacy of treatment for steroid-resistant aGVHD
time frame: 1 year
description: The responses to aGVHD are according to the literature criteria, including completely response (CR), partial response (PR) and no response (NR), and CR is defined as resolution of all symptoms of aGVHD; PR is defined as a decrease by at least 1 GVHD stage in any 1 organ system without deterioration in others 24. Overall response (OR) includes CR and PR.
measure: Incidence of infections
time frame: 1 year
description: Infections are mainly focused on cytomegalovirus (CMV) and Epstein-Barr virus ( EBV) infections during study treatments and within one year after study treatments.
measure: Incidence of primary underlying disease relapse
time frame: 1 year
measure: Incidence of chronic GVHD
time frame: 1 year
arm group label: Mesenchymal stem cells
arm group type: Experimental
description: MSCs will be given at a median dose of 1×10^6 cells/kg once weekly for 4 dose (as 1 cycle) or until CR. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. Besides, CD25 monoclonal antibody (20mg/kg) will be administered at day 1,4,8,15, 21 and calcineurin inhibitors will also be used.
arm group label: CD25 Mc Ab & calcineurin inhibitors
arm group type: Experimental
description: CD25 monoclonal antibody (20mg/kg, day 1,4,8,15,21) will be administered combined with calcineurin inhibitors. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given.
intervention type: Drug
intervention name: CD25 monoclonal antibody
arm group label: CD25 Mc Ab & calcineurin inhibitors
arm group label: Mesenchymal stem cells
intervention type: Drug
intervention name: calcineurin inhibitors
arm group label: CD25 Mc Ab & calcineurin inhibitors
arm group label: Mesenchymal stem cells
intervention type: Biological
intervention name: MSCs
arm group label: Mesenchymal stem cells
criteria: 
gender: All
minimum age: 14 Years
maximum age: 65 Years
healthy volunteers: No
last name: Qifa Liu, MD
role: Principal Investigator
affiliation: Nanfang Hospital, Southern Medical University
last name: Ren Lin
phone: +86-020-62787883
email: lansinglinren@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.
PMID: 15121408
citation: Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Diez Campelo M, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011 Jul;96(7):1072-6. doi: 10.3324/haematol.2010.038356. Epub 2011 Mar 10.
PMID: 21393326
responsible party type: Principal Investigator
investigator affiliation: Nanfang Hospital, Southern Medical University
investigator full name: Qifa Liu
investigator title: Professor
mesh term: Graft vs Host Disease
mesh term: Antibodies
mesh term: Antibodies, Monoclonal
mesh term: Calcineurin Inhibitors