<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/NCT03246178</url>
  </required_header>
  <id_info>
    <org_study_id>2016QX-KS008</org_study_id>
    <nct_id>NCT03246178</nct_id>
  </id_info>
  <brief_title>Haploidentical Transplantation in Severe Aplastic Anemia</brief_title>
  <official_title>A Research on Haploidentical Transplantation in Severe Aplastic Anemia Using Reduced-intensity Fludarabine-based Conditioning</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wu Xiaoxiong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese PLA General 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 prospective case-control study on SAA patients treated with HSCT, order to further&#xD;
      discuss and assess the safety, feasibility and effectiveness of HFD-HSCT which performed with&#xD;
      reduced-intensity fludarabine-based conditioning regimen.Our findings would indicate that SAA&#xD;
      patients who lack MSD benefited most if HFD-HSCT was performed with reduced-intensity&#xD;
      fludarabine-based conditioning regimen, and our improved outcomes with HFD-HSCT may lead to a&#xD;
      salvaged therapy and an expanded direct role for SAA in the future.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">July 10, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients with SAA</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>no masking</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Engraftment</measure>
    <time_frame>In the first months after infusion</time_frame>
    <description>Neutrophil engraftment was defined as the first of three consecutive days in which the neutrophil counts (ANC) exceeded 0.50 × 109/L, and platelet engraftment was defined as the first of five consecutive days in which the platelet count exceeded 20 × 109/L without transfusion. GF was classified as follows: (1) primary non-engraftment (failure to reach a neutrophil count of 0.5×109/L after transplant); (2) rejection (decrease in blood counts to &lt; 0.5×109/L neutrophils, after achieving a neutrophil count of 0.5×109/L); (3) late graft failure (decrease of blood counts after day 100 to &lt; 1.0×109/L neutrophils and &lt; 30×109/L platelets).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Toxicity grading</measure>
    <time_frame>TRT was defined as toxic effects occurring within 40 days after HSCT</time_frame>
    <description>The transplantation-related toxicity (TRT) was graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. Organ damage due to GVHD or infectious complications were excluded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chimerism analyses +30</measure>
    <time_frame>Days +30 after HSCT</time_frame>
    <description>Chimerism would be evaluated in recipient BM cells usually on days +30 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chimerism analyses +100</measure>
    <time_frame>Days +100 after HSCT</time_frame>
    <description>Chimerism would be evaluated in recipient BM cells usually on days +180 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chimerism analyses +180</measure>
    <time_frame>Days +180 after HSCT</time_frame>
    <description>Chimerism would be evaluated in recipient BM cells usually on days +100 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chimerism analyses +365</measure>
    <time_frame>Days +365 after HSCT</time_frame>
    <description>Chimerism would be evaluated in recipient BM cells usually on days +365 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS 1-year</measure>
    <time_frame>1-year after HSCT</time_frame>
    <description>OS was defined as the time from transplantation to death from any cause or the last follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS 2-year</measure>
    <time_frame>2-year after HSCT</time_frame>
    <description>OS was defined as the time from transplantation to death from any cause or the last follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS 5-year</measure>
    <time_frame>5-year after HSCT</time_frame>
    <description>OS was defined as the time from transplantation to death from any cause or the last follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>EFS 1-year</measure>
    <time_frame>1-year after HSCT</time_frame>
    <description>EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.&#xD;
EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>EFS 2-year</measure>
    <time_frame>2-year after HSCT</time_frame>
    <description>EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>EFS 5-year</measure>
    <time_frame>5-year after HSCT</time_frame>
    <description>EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Severe Aplastic Anemia</condition>
  <arm_group>
    <arm_group_label>MSD-HSCT</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This group received treatment of matched sibling donor - hematopoietic stem cell transplantation (MSD-HSCT).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HFD-HSCT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group received treatment of haploid family donor - hematopoietic stem cell transplantation (HFD-HSCT).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MSD-HSCT</intervention_name>
    <description>Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC≥25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 30mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan;&#xD;
Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight;&#xD;
Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 150-250 ng/ml. The oral MMF dose was 20 mg/kg/day from day -1 and was tapered off after 1 months if no aGVHD was observed.</description>
    <arm_group_label>MSD-HSCT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HFD-HSCT</intervention_name>
    <description>Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC≥25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 35mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan;&#xD;
Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight;&#xD;
Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 200-300 ng/ml. The oral MMF dose was 20 mg/kg/day from day -3 and was tapered off after 2 months if no aGVHD was observed.</description>
    <arm_group_label>HFD-HSCT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        (i) Diagnosis of SAA, very SAA or SAA and paroxysmal nocturnal hemoglobinuria (PNH)&#xD;
        according to the International Aplastic Anemia Study Group; (ii) SAA patients no response&#xD;
        to previous IST; (iii) adequate performance status [Eastern Cooperative Oncology Group&#xD;
        (ECOG) score 0-2].&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        (i) Congenital forms of aplastic anemia; (ii)Patients with any severe pulmonary, cardiac,&#xD;
        liver, or renal diseases or active infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaoxiong WU, PhD</last_name>
    <role>Study Director</role>
    <affiliation>The First Affiliated Hospital of General Hospital of PLA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Hematology, 304th Clinical Division, Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100048</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>May 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>August 8, 2017</last_update_submitted>
  <last_update_submitted_qc>August 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Wu Xiaoxiong</investigator_full_name>
    <investigator_title>Head, Research group of the Center of Hematology</investigator_title>
  </responsible_party>
  <keyword>Haploidentical</keyword>
  <keyword>Hematopoietic stem cell transplantation</keyword>
  <keyword>Severe aplastic anemia</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>
  <!-- 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/NCT03246178
org study id: 2016QX-KS008
nct id: NCT03246178
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a prospective case-control study on SAA patients treated with HSCT, order to further
      discuss and assess the safety, feasibility and effectiveness of HFD-HSCT which performed with
      reduced-intensity fludarabine-based conditioning regimen.Our findings would indicate that SAA
      patients who lack MSD benefited most if HFD-HSCT was performed with reduced-intensity
      fludarabine-based conditioning regimen, and our improved outcomes with HFD-HSCT may lead to a
      salvaged therapy and an expanded direct role for SAA in the future.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients with SAA
primary purpose: Treatment
masking: None (Open Label)
masking description: no masking
measure: Engraftment
time frame: In the first months after infusion
description: Neutrophil engraftment was defined as the first of three consecutive days in which the neutrophil counts (ANC) exceeded 0.50 × 109/L, and platelet engraftment was defined as the first of five consecutive days in which the platelet count exceeded 20 × 109/L without transfusion. GF was classified as follows: (1) primary non-engraftment (failure to reach a neutrophil count of 0.5×109/L after transplant); (2) rejection (decrease in blood counts to < 0.5×109/L neutrophils, after achieving a neutrophil count of 0.5×109/L); (3) late graft failure (decrease of blood counts after day 100 to < 1.0×109/L neutrophils and < 30×109/L platelets).
measure: Toxicity grading
time frame: TRT was defined as toxic effects occurring within 40 days after HSCT
description: The transplantation-related toxicity (TRT) was graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. Organ damage due to GVHD or infectious complications were excluded.
measure: Chimerism analyses +30
time frame: Days +30 after HSCT
description: Chimerism would be evaluated in recipient BM cells usually on days +30 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.
measure: Chimerism analyses +100
time frame: Days +100 after HSCT
description: Chimerism would be evaluated in recipient BM cells usually on days +180 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.
measure: Chimerism analyses +180
time frame: Days +180 after HSCT
description: Chimerism would be evaluated in recipient BM cells usually on days +100 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.
measure: Chimerism analyses +365
time frame: Days +365 after HSCT
description: Chimerism would be evaluated in recipient BM cells usually on days +365 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.
measure: OS 1-year
time frame: 1-year after HSCT
description: OS was defined as the time from transplantation to death from any cause or the last follow-up.
measure: OS 2-year
time frame: 2-year after HSCT
description: OS was defined as the time from transplantation to death from any cause or the last follow-up.
measure: OS 5-year
time frame: 5-year after HSCT
description: OS was defined as the time from transplantation to death from any cause or the last follow-up.
measure: EFS 1-year
time frame: 1-year after HSCT
description: EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.
EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.
measure: EFS 2-year
time frame: 2-year after HSCT
description: EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.
measure: EFS 5-year
time frame: 5-year after HSCT
description: EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.
arm group label: MSD-HSCT
arm group type: Other
description: This group received treatment of matched sibling donor - hematopoietic stem cell transplantation (MSD-HSCT).
arm group label: HFD-HSCT
arm group type: Experimental
description: This group received treatment of haploid family donor - hematopoietic stem cell transplantation (HFD-HSCT).
intervention type: Other
intervention name: MSD-HSCT
description: Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC≥25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 30mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan;
Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight;
Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 150-250 ng/ml. The oral MMF dose was 20 mg/kg/day from day -1 and was tapered off after 1 months if no aGVHD was observed.
arm group label: MSD-HSCT
intervention type: Other
intervention name: HFD-HSCT
description: Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC≥25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 35mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan;
Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight;
Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 200-300 ng/ml. The oral MMF dose was 20 mg/kg/day from day -3 and was tapered off after 2 months if no aGVHD was observed.
arm group label: HFD-HSCT
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Xiaoxiong WU, PhD
role: Study Director
affiliation: The First Affiliated Hospital of General Hospital of PLA
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Wu Xiaoxiong
investigator title: Head, Research group of the Center of Hematology
mesh term: Anemia
mesh term: Anemia, Aplastic