<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/NCT02240992</url>
  </required_header>
  <id_info>
    <org_study_id>NFH-PBSC-MSC-PGF-2014</org_study_id>
    <nct_id>NCT02240992</nct_id>
  </id_info>
  <brief_title>MSCs With or Without Peripheral Blood Stem Cell for Treatment of Poor Graft Function and Delayed Platelet Engraftment</brief_title>
  <official_title>Mesenchymal Stem Cells With or Without G-CSF Mobilized Peripheral Blood Stem Cell for Treatment of Poor Graft Function and Delayed Platelet Engraftment After Allogeneic Hematopoietic Stem Cell Transplant</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 mesenchymal stem cells (MSCs) with or&#xD;
      without granulocyte colony-stimulating factor (G-CSF) mobilized peripheral stem cells (PBSC)&#xD;
      in treating patients experiencing poor graft function or delayed platelet engraftment after&#xD;
      allogeneic hematopoietic stem cell transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the only cure for many&#xD;
      hematologic diseases. However, about 5-27% of patients would suffer from poor graft function&#xD;
      (PGF) and more recipients might develop delayed platelet engraftment (DPE) after allo-HSCT.&#xD;
      These complications are associated with considerable mortality related to infections or&#xD;
      hemorrhagic complications. Treatment of PGF and DPE usually involves hematopoietic growth&#xD;
      factors such as granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO), or&#xD;
      second transplantation, but these methods have dismal effect or even a significant risk of&#xD;
      graft-versus-host disease (GVHD).&#xD;
&#xD;
      Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated&#xD;
      from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs&#xD;
      include improving hematopoietic engraftment, preventing and treating graft-versus-host&#xD;
      disease after allo-HSCT and so on. Some studies have shown that MSCs combined with PBSC or&#xD;
      cord blood could be useful to improve engraftment after HSCT. Several reports suggested MSCs&#xD;
      might be effective in the treatment of PGF.&#xD;
&#xD;
      However, the efficacy of MSCs as single-drug treatment for PGF or DPE is unsatisfactory in&#xD;
      our previous study. Therefore, in the present study, G-CSF mobilized PBSC will be used&#xD;
      combined with MSCs in the patients with PGF or DPE after allo-HSCT.&#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>Percentage of Participants with Hematopoietic Recovery</measure>
    <time_frame>1 year</time_frame>
    <description>Hematopoietic reconstitution post-transplantation is defined as reconstitution of both neutrophil and platelet numbers. Neutrophil reconstitution is defined as occurring on the first 3 consecutive days with an neutrophil(NEU)&gt;0.5×10^9/L, and platelet (PLT) reconstitution is defined as the first &gt;20×10^9/L for 3 consecutive days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft-versus-host disease</measure>
    <time_frame>1 year</time_frame>
    <description>Graft-versus-host disease (GVHD) includes acute GVHD and chronic GVHD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of infections</measure>
    <time_frame>1 year</time_frame>
    <description>Infections include bacterial, invasive fungal and viral infections</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 acute toxicity</measure>
    <time_frame>up to 100 days</time_frame>
    <description>Acute toxicity mainly involves the heart,live and kidney.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Stem Cell Transplantation, Hematopoietic</condition>
  <condition>Poor Graft Function</condition>
  <condition>Delayed Platelet Engraftment</condition>
  <condition>Hematological Diseases</condition>
  <arm_group>
    <arm_group_label>MSCs&amp;PBSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PBSC will be intravenously infused at a dose of 2×10^8/kg. MSCs will be intravenously infused at a dose of 1×10^6 cells/kg once per week or until complete response(CR) . If the patients do not achieve CR or partial remission (PR) within 4 weeks, they will swithed to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MSCs will be intravenously infused at a dose of 1×10^6 cells/kg once per week or until CR. If the patients have no response (NR) within 4 weeks, they will switch to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PBSC</intervention_name>
    <arm_group_label>MSCs&amp;PBSC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MSCs</intervention_name>
    <arm_group_label>MSCs</arm_group_label>
    <arm_group_label>MSCs&amp;PBSC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age：14-65 years&#xD;
&#xD;
          -  PGF or DPE after allo-HSCT&#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, MD</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>Sanchez-Guijo FM, Lopez-Villar O, Lopez-Anglada L, Villaron EM, Muntion S, Diez-Campelo M, Perez-Simon JA, San Miguel JF, Caballero D, del Canizo MC. Allogeneic mesenchymal stem cell therapy for refractory cytopenias after hematopoietic stem cell transplantation. Transfusion. 2012 May;52(5):1086-91. doi: 10.1111/j.1537-2995.2011.03400.x. Epub 2011 Oct 24.</citation>
    <PMID>22023454</PMID>
  </reference>
  <reference>
    <citation>Meuleman N, Tondreau T, Ahmad I, Kwan J, Crokaert F, Delforge A, Dorval C, Martiat P, Lewalle P, Lagneaux L, Bron D. Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study. Stem Cells Dev. 2009 Nov;18(9):1247-52. doi: 10.1089/scd.2009.0029.</citation>
    <PMID>19309241</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>Poor Graft Function</keyword>
  <keyword>Delayed platelet engraftment</keyword>
  <keyword>Peripheral Blood Stem Cell</keyword>
  <keyword>Mesenchymal Stem Cells</keyword>
  <keyword>Allogeneic hematopoietic stem cell transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematologic Diseases</mesh_term>
  </condition_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/NCT02240992
org study id: NFH-PBSC-MSC-PGF-2014
nct id: NCT02240992
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 mesenchymal stem cells (MSCs) with or
      without granulocyte colony-stimulating factor (G-CSF) mobilized peripheral stem cells (PBSC)
      in treating patients experiencing poor graft function or delayed platelet engraftment after
      allogeneic hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the only cure for many
      hematologic diseases. However, about 5-27% of patients would suffer from poor graft function
      (PGF) and more recipients might develop delayed platelet engraftment (DPE) after allo-HSCT.
      These complications are associated with considerable mortality related to infections or
      hemorrhagic complications. Treatment of PGF and DPE usually involves hematopoietic growth
      factors such as granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO), or
      second transplantation, but these methods have dismal effect or even a significant risk of
      graft-versus-host disease (GVHD).

      Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated
      from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs
      include improving hematopoietic engraftment, preventing and treating graft-versus-host
      disease after allo-HSCT and so on. Some studies have shown that MSCs combined with PBSC or
      cord blood could be useful to improve engraftment after HSCT. Several reports suggested MSCs
      might be effective in the treatment of PGF.

      However, the efficacy of MSCs as single-drug treatment for PGF or DPE is unsatisfactory in
      our previous study. Therefore, in the present study, G-CSF mobilized PBSC will be used
      combined with MSCs in the patients with PGF or DPE after allo-HSCT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants with Hematopoietic Recovery
time frame: 1 year
description: Hematopoietic reconstitution post-transplantation is defined as reconstitution of both neutrophil and platelet numbers. Neutrophil reconstitution is defined as occurring on the first 3 consecutive days with an neutrophil(NEU)>0.5×10^9/L, and platelet (PLT) reconstitution is defined as the first >20×10^9/L for 3 consecutive days.
measure: Incidence of graft-versus-host disease
time frame: 1 year
description: Graft-versus-host disease (GVHD) includes acute GVHD and chronic GVHD.
measure: Incidence of infections
time frame: 1 year
description: Infections include bacterial, invasive fungal and viral infections
measure: Incidence of primary underlying disease relapse
time frame: 1 year
measure: Incidence of acute toxicity
time frame: up to 100 days
description: Acute toxicity mainly involves the heart,live and kidney.
arm group label: MSCs&PBSC
arm group type: Experimental
description: PBSC will be intravenously infused at a dose of 2×10^8/kg. MSCs will be intravenously infused at a dose of 1×10^6 cells/kg once per week or until complete response(CR) . If the patients do not achieve CR or partial remission (PR) within 4 weeks, they will swithed to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.
arm group label: MSCs
arm group type: Experimental
description: MSCs will be intravenously infused at a dose of 1×10^6 cells/kg once per week or until CR. If the patients have no response (NR) within 4 weeks, they will switch to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.
intervention type: Biological
intervention name: PBSC
arm group label: MSCs&PBSC
intervention type: Biological
intervention name: MSCs
arm group label: MSCs
arm group label: MSCs&PBSC
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, MD
phone: +86-020-62787883
email: lansinglinren@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Sanchez-Guijo FM, Lopez-Villar O, Lopez-Anglada L, Villaron EM, Muntion S, Diez-Campelo M, Perez-Simon JA, San Miguel JF, Caballero D, del Canizo MC. Allogeneic mesenchymal stem cell therapy for refractory cytopenias after hematopoietic stem cell transplantation. Transfusion. 2012 May;52(5):1086-91. doi: 10.1111/j.1537-2995.2011.03400.x. Epub 2011 Oct 24.
PMID: 22023454
citation: Meuleman N, Tondreau T, Ahmad I, Kwan J, Crokaert F, Delforge A, Dorval C, Martiat P, Lewalle P, Lagneaux L, Bron D. Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study. Stem Cells Dev. 2009 Nov;18(9):1247-52. doi: 10.1089/scd.2009.0029.
PMID: 19309241
responsible party type: Principal Investigator
investigator affiliation: Nanfang Hospital, Southern Medical University
investigator full name: Qifa Liu
investigator title: Professor
mesh term: Hematologic Diseases