<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/NCT03828071</url>
  </required_header>
  <id_info>
    <org_study_id>NJCT-1008</org_study_id>
    <nct_id>NCT03828071</nct_id>
  </id_info>
  <brief_title>Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis</brief_title>
  <official_title>National Clinical Research Center of Kidney Diseases, Jinling Hospital</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanjing University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanjing University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, we aimed to evaluate the long term efficacy, remission, survival and safety of&#xD;
      autologous hematopoietic stem cell transplantation in patients with refractory lupus&#xD;
      nephritis.&#xD;
&#xD;
      This is an single arm, non-randomized study. Patients who were diagnosed with relapsed and&#xD;
      refractory lupus nephritis would included in this study. Refractory lupus nephritis is&#xD;
      defined as no response to at least one type of immunosuppressant therapy (including&#xD;
      corticosteroids, cyclophosphamide, tacrolimus, mycophenolate mofetil and cyclosporine) for&#xD;
      more than six months, or relapse during the period maintenance therapy with kidney&#xD;
      pathological transformation or persistently positive antibodies. Close observation was&#xD;
      carried out at stem cell harvest, at transplantation, at 3, 6, 12, 18, and 24 months and then&#xD;
      once a year after autologous stem cell transplantation.&#xD;
&#xD;
      20-30 cases will be included in this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment plan: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2)&#xD;
      for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was&#xD;
      administered when the level of peripheral leucocytes was &lt; 1×109/L. Peripheral leukocyte&#xD;
      counts were monitored, and harvesting was performed when the peripheral white blood cell&#xD;
      level rebounded (usually 11 days after cyclophosphamide). The target acquisition was CD34+&#xD;
      cells &gt; 2×10^6/kg and mononuclear cells &gt; 2×10^8/kg. The graft was preserved at a temperature&#xD;
      of -196 ℃ for further use. The conditioning regimen consisted of intravenous cyclophosphamide&#xD;
      (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit&#xD;
      antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose&#xD;
      of cyclophosphamide and ATG could be reduced according to the patients' condition.&#xD;
      Methylprednisolone (80-500 mg/day) was administered through intravenous drip at the same time&#xD;
      with ATG to reduce anaphylaxis. The incidence of drug-related complications was decreased by&#xD;
      hyperhydration (the volume of infusion liquid is 50 ml/kg/day), urine alkalization (infusion&#xD;
      of sodium bicarbonate 250ml/day), and anti-emetic medication. G-CSF (0.5 μg/kg/d) was&#xD;
      administered to each patient beginning the day after stem cells reinfusion until the level of&#xD;
      absolute peripheral neutrophil count was consecutively higher than 1.0 × 10^9/L.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2011</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">January 1, 2015</primary_completion_date>
  <phase>N/A</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>Renal remission rate</measure>
    <time_frame>seven years</time_frame>
    <description>The curative effect on the kidney was defined as follows: complete remission: proteinuria&lt; 0.4 g/24 h, red blood cell (RBC) &lt; 3/HP in urine sediment, serum albumin &gt; 3.5g/dl and serum creatinine &lt; 1.24 mg/dl; partial remission: 50% baseline &lt; decrease of proteinuria &lt; 3.5 g/24 h, serum albumin &gt;30g/L and serum creatinine &lt; 1.24 mg/dl, no remission (NR): failed to achieve partial remission</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>renal survival</measure>
    <time_frame>seven years</time_frame>
    <description>the time from treatment start to dialysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>treatment related mortality</measure>
    <time_frame>3 months</time_frame>
    <description>patients who dies in 3 months after treatment start.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Lupus Nephritis</condition>
  <arm_group>
    <arm_group_label>stem cell transplantation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>patients enrolled in this study will received autologous hematopoietic stem cell transplantation as the initial treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Autologous hematopoietic stem cell transplantation</intervention_name>
    <description>Stem cell mobilization and collection: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was administered when the level of peripheral leucocytes was &lt; 1×109/L. Peripheral leukocyte counts were monitored, and harvesting was performed when the peripheral white blood cell level rebounded .&#xD;
Conditioning and reinfusion of stem cells: The conditioning regimen consisted of intravenous cyclophosphamide (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose of cyclophosphamide and ATG could be reduced according to the patients' condition.</description>
    <arm_group_label>stem cell transplantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Diagnosed with relapsed and refractory lupus nephritis; 2. Ages from 14 - 45 years&#xD;
             old; 3. Serum creatinine &lt; 2mg/dl; 4. Alanine aminotransferase &lt; 2 times of normal&#xD;
             upper limit; 5. Left ventricular ejection fraction &gt; 50%; 6. Subjects (or their legal&#xD;
             representatives) must signed an informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Active infection; 2. Known or suspected hypersensitivity to CTX or ATG; 3. Subjects&#xD;
             suffering from uncontrolled or severe cardiovascular disease; 4. Subjects suffering&#xD;
             from serious physical disease and mental illnesses.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>zhihong liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Clinical Research Center of Kidney Diseases, Jinling Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Clinical Research Center of Kidney Diseases, Jinling Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210002</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanjing University School of Medicine</investigator_affiliation>
    <investigator_full_name>Zhi-Hong Liu, M.D.</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephritis</mesh_term>
    <mesh_term>Lupus Nephritis</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/NCT03828071
org study id: NJCT-1008
nct id: NCT03828071
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
In this study, we aimed to evaluate the long term efficacy, remission, survival and safety of
      autologous hematopoietic stem cell transplantation in patients with refractory lupus
      nephritis.

      This is an single arm, non-randomized study. Patients who were diagnosed with relapsed and
      refractory lupus nephritis would included in this study. Refractory lupus nephritis is
      defined as no response to at least one type of immunosuppressant therapy (including
      corticosteroids, cyclophosphamide, tacrolimus, mycophenolate mofetil and cyclosporine) for
      more than six months, or relapse during the period maintenance therapy with kidney
      pathological transformation or persistently positive antibodies. Close observation was
      carried out at stem cell harvest, at transplantation, at 3, 6, 12, 18, and 24 months and then
      once a year after autologous stem cell transplantation.

      20-30 cases will be included in this study.
Treatment plan: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2)
      for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was
      administered when the level of peripheral leucocytes was < 1×109/L. Peripheral leukocyte
      counts were monitored, and harvesting was performed when the peripheral white blood cell
      level rebounded (usually 11 days after cyclophosphamide). The target acquisition was CD34+
      cells > 2×10^6/kg and mononuclear cells > 2×10^8/kg. The graft was preserved at a temperature
      of -196 ℃ for further use. The conditioning regimen consisted of intravenous cyclophosphamide
      (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit
      antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose
      of cyclophosphamide and ATG could be reduced according to the patients' condition.
      Methylprednisolone (80-500 mg/day) was administered through intravenous drip at the same time
      with ATG to reduce anaphylaxis. The incidence of drug-related complications was decreased by
      hyperhydration (the volume of infusion liquid is 50 ml/kg/day), urine alkalization (infusion
      of sodium bicarbonate 250ml/day), and anti-emetic medication. G-CSF (0.5 μg/kg/d) was
      administered to each patient beginning the day after stem cells reinfusion until the level of
      absolute peripheral neutrophil count was consecutively higher than 1.0 × 10^9/L.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Renal remission rate
time frame: seven years
description: The curative effect on the kidney was defined as follows: complete remission: proteinuria< 0.4 g/24 h, red blood cell (RBC) < 3/HP in urine sediment, serum albumin > 3.5g/dl and serum creatinine < 1.24 mg/dl; partial remission: 50% baseline < decrease of proteinuria < 3.5 g/24 h, serum albumin >30g/L and serum creatinine < 1.24 mg/dl, no remission (NR): failed to achieve partial remission
measure: renal survival
time frame: seven years
description: the time from treatment start to dialysis.
measure: treatment related mortality
time frame: 3 months
description: patients who dies in 3 months after treatment start.
arm group label: stem cell transplantation
arm group type: Other
description: patients enrolled in this study will received autologous hematopoietic stem cell transplantation as the initial treatment.
intervention type: Procedure
intervention name: Autologous hematopoietic stem cell transplantation
description: Stem cell mobilization and collection: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was administered when the level of peripheral leucocytes was < 1×109/L. Peripheral leukocyte counts were monitored, and harvesting was performed when the peripheral white blood cell level rebounded .
Conditioning and reinfusion of stem cells: The conditioning regimen consisted of intravenous cyclophosphamide (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose of cyclophosphamide and ATG could be reduced according to the patients' condition.
arm group label: stem cell transplantation
criteria: 
gender: All
minimum age: 14 Years
maximum age: 45 Years
healthy volunteers: No
last name: zhihong liu, MD
role: Principal Investigator
affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Nanjing University School of Medicine
investigator full name: Zhi-Hong Liu, M.D.
investigator title: Director
mesh term: Nephritis
mesh term: Lupus Nephritis