<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/NCT02199301</url>
  </required_header>
  <id_info>
    <org_study_id>2010-07-210</org_study_id>
    <nct_id>NCT02199301</nct_id>
  </id_info>
  <brief_title>Tolerance Induction in Living Donor Kidney Transplantation With Hematopoietic Stem Cell Transplantation</brief_title>
  <official_title>Tolerance Induction in Living Donor Kidney Transplantation With Hematopoietic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samsung Medical Center</source>
  <brief_summary>
    <textblock>
      Kidney transplantation (KT) requires a life-long immune suppression (IS). It has been&#xD;
      well-known that long-term IS inevitably causes various complication e.g. infection, toxicity,&#xD;
      diabetes, osteoporosis, avascular necrosis of hip joint, cataract, acne, and malignancies and&#xD;
      so on. Tolerance induction showing graft function without maintenance IS has been considered&#xD;
      as a final solution in the transplantation recipients. Tolerance induction can be achieved in&#xD;
      KT recipients with donor hematopoietic stem cell transplantation (HSCT).&#xD;
&#xD;
      In this study, adult patients (18 and more years of age) with a human leukocyte antigen&#xD;
      (HLA)-haplotype match donor are enrolled. Patients receive preconditioning treatment for HSCT&#xD;
      1week prior to KT. Bone marrow is harvested from donor under general anesthesia at the time&#xD;
      of nephrectomy for transplantation in donor. Donor BM is infused immediate&#xD;
      post-transplantation at intensive care unit (ICU). Immunologic measurements including&#xD;
      microchimerism study and protocol biopsy will be followed at several time points. IS will be&#xD;
      tapered slowly and withdrawn over a period of several months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2011</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 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>Immune Suppression Withdrawal</measure>
    <time_frame>Immune Suppression Withdrawal within 18 months post-transplantation</time_frame>
    <description>Immune suppression will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Graft failure</measure>
    <time_frame>At the post-transplantation 18 months</time_frame>
    <description>In this study, immune suppression(IS) will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements. At the post-transplantation 18 months we evaluate graft failure episode irrespective of IS withdrawal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Allograft Rejection</measure>
    <time_frame>At the post-transplantation 18 months</time_frame>
    <description>In this study, immune suppression(IS) will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements. At the post-transplantation 18 months we evaluate allograft rejection episode irrespective of IS withdrawal.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Microchimerism</measure>
    <time_frame>At post-transplantation 1, 2, 3, 4, 8, and 24 wks</time_frame>
    <description>Presence and proportion of microchimerism in recipient's peripheral blood will be measured by microsatellite short tandem repeat.</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Cell Profiling</measure>
    <time_frame>At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks</time_frame>
    <description>Changes of proportion or absolute count of immune cells are measured by flowcytometric analysis in recipient's peripheral blood, using cluster of differentiation (CD) marker.</description>
  </other_outcome>
  <other_outcome>
    <measure>Mixed Lymphocyte Reaction</measure>
    <time_frame>At post-transplantation 8, 24, 52 weeks</time_frame>
    <description>Mixed lymphocyte reaction will be done for the evaluation for the donor-specific immune response (Donor vs. 3rd party) in vitro.</description>
  </other_outcome>
  <other_outcome>
    <measure>Protocol Biopsy</measure>
    <time_frame>Post-transplantation 3, 24, and 52 weeks</time_frame>
    <description>Absence or presence of allograft rejection is confirmed by ultrasonography-guided percutaneous biopsy during follow-up and prior to withdrawal of immunosuppressive agent.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">6</enrollment>
  <condition>End Stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>BMTKT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transplantation Conditioning for BMT</intervention_name>
    <description>Transplantation Conditioning for BMT (POD#-7~-1) POD#-7: Rituximab (Mabthera, Roche Pharma Aktiengesellschaft (AG) Swiss) 375/m2 iv infusion POD#-6~-3: Fludarabine (Fludara Inj., Bayer AG, Germany) 30mg/m2/day iv infusion POD#-5~-4: Cyclophosphamide (Endoxan Inj., Baxter Oncology Gesellschaft mit beschränkter Haftung (GmbH), Germany) 30mg/kg/day iv infusion POD#-2: (Rituximab 375/m2 iv infusion) POD#-1: Thymic irradiation (Dose, 700cGy)</description>
    <arm_group_label>BMTKT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All consenting adult (18 and more years of age) living donor kidney transplant&#xD;
             recipients who have a one haplotype match donor.&#xD;
&#xD;
          2. Patients who have no known contraindication to administration of rabbit anti-thymocyte&#xD;
             globulin (ATG) or radiation.&#xD;
&#xD;
          3. Patients who agree to participate in the study and sign an Informed Consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of previous episode of transplantation including kidney&#xD;
&#xD;
          2. Simultaneous multi-visceral transplantation&#xD;
&#xD;
          3. Demonstration of donor specific antibody (DSA) or panel reactive antibody(PRA) greater&#xD;
             than 20%&#xD;
&#xD;
          4. ABO blood type incompatible&#xD;
&#xD;
          5. Previous treatment with rabbit anti-thymocyte globulin or a known allergy to rabbit&#xD;
             proteins.&#xD;
&#xD;
          6. History of malignancy with the exception of non-melanoma skin malignancies.&#xD;
&#xD;
          7. Uncontrolled systemic or concomitant unstable infection&#xD;
&#xD;
          8. Serological evidence of Hepatitis B or Hepatitis C or HIV infection.&#xD;
&#xD;
          9. Severe psychiatric disease&#xD;
&#xD;
         10. Leukopenia (with a white blood cell count &lt; 3000/mm3)&#xD;
&#xD;
         11. Disagreement to participate in the study and sign an Informed Consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Sung Joo Kim, MD, PhD</last_name>
    <phone>82-2-3410-3476</phone>
    <email>kmhyj.kim@samsung.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jae Berm Park, MD, PhD</last_name>
    <phone>82-2-3410-3647</phone>
    <email>jbparkmd@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Samsung Medical Center, Organ Transplant Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sung Joo Kim, MD, PhD</last_name>
      <phone>82-2-3410-3476</phone>
      <email>kmhyj.kim@samsung.com</email>
    </contact>
    <contact_backup>
      <last_name>Jae Berm Park, MD, PhD</last_name>
      <phone>82-2-3410-3647</phone>
      <email>jbparkmd@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Sung Joo Kim, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jae Berm Park, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 10, 2012</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>July 22, 2014</last_update_submitted>
  <last_update_submitted_qc>July 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 24, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Kidney transplantation</keyword>
  <keyword>Tolerance induction</keyword>
  <keyword>Immunosuppression withdrawal</keyword>
  <keyword>Bone marrow transplantation</keyword>
  <keyword>Transplantation conditioning</keyword>
  <keyword>Hematopoietic stem cell transplantation</keyword>
  <keyword>Living donor</keyword>
  <keyword>Haplotype</keyword>
  <keyword>Immune tolerance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</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/NCT02199301
org study id: 2010-07-210
nct id: NCT02199301
lead sponsor: 
Kidney transplantation (KT) requires a life-long immune suppression (IS). It has been
      well-known that long-term IS inevitably causes various complication e.g. infection, toxicity,
      diabetes, osteoporosis, avascular necrosis of hip joint, cataract, acne, and malignancies and
      so on. Tolerance induction showing graft function without maintenance IS has been considered
      as a final solution in the transplantation recipients. Tolerance induction can be achieved in
      KT recipients with donor hematopoietic stem cell transplantation (HSCT).

      In this study, adult patients (18 and more years of age) with a human leukocyte antigen
      (HLA)-haplotype match donor are enrolled. Patients receive preconditioning treatment for HSCT
      1week prior to KT. Bone marrow is harvested from donor under general anesthesia at the time
      of nephrectomy for transplantation in donor. Donor BM is infused immediate
      post-transplantation at intensive care unit (ICU). Immunologic measurements including
      microchimerism study and protocol biopsy will be followed at several time points. IS will be
      tapered slowly and withdrawn over a period of several months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Immune Suppression Withdrawal
time frame: Immune Suppression Withdrawal within 18 months post-transplantation
description: Immune suppression will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements.
measure: Graft failure
time frame: At the post-transplantation 18 months
description: In this study, immune suppression(IS) will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements. At the post-transplantation 18 months we evaluate graft failure episode irrespective of IS withdrawal.
measure: Allograft Rejection
time frame: At the post-transplantation 18 months
description: In this study, immune suppression(IS) will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements. At the post-transplantation 18 months we evaluate allograft rejection episode irrespective of IS withdrawal.
measure: Microchimerism
time frame: At post-transplantation 1, 2, 3, 4, 8, and 24 wks
description: Presence and proportion of microchimerism in recipient's peripheral blood will be measured by microsatellite short tandem repeat.
measure: Immune Cell Profiling
time frame: At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks
description: Changes of proportion or absolute count of immune cells are measured by flowcytometric analysis in recipient's peripheral blood, using cluster of differentiation (CD) marker.
measure: Mixed Lymphocyte Reaction
time frame: At post-transplantation 8, 24, 52 weeks
description: Mixed lymphocyte reaction will be done for the evaluation for the donor-specific immune response (Donor vs. 3rd party) in vitro.
measure: Protocol Biopsy
time frame: Post-transplantation 3, 24, and 52 weeks
description: Absence or presence of allograft rejection is confirmed by ultrasonography-guided percutaneous biopsy during follow-up and prior to withdrawal of immunosuppressive agent.
arm group label: BMTKT
arm group type: Experimental
description: Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT)
intervention type: Procedure
intervention name: Transplantation Conditioning for BMT
description: Transplantation Conditioning for BMT (POD#-7~-1) POD#-7: Rituximab (Mabthera, Roche Pharma Aktiengesellschaft (AG) Swiss) 375/m2 iv infusion POD#-6~-3: Fludarabine (Fludara Inj., Bayer AG, Germany) 30mg/m2/day iv infusion POD#-5~-4: Cyclophosphamide (Endoxan Inj., Baxter Oncology Gesellschaft mit beschränkter Haftung (GmbH), Germany) 30mg/kg/day iv infusion POD#-2: (Rituximab 375/m2 iv infusion) POD#-1: Thymic irradiation (Dose, 700cGy)
arm group label: BMTKT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sung Joo Kim, MD, PhD
phone: 82-2-3410-3476
email: kmhyj.kim@samsung.com
last name: Jae Berm Park, MD, PhD
phone: 82-2-3410-3647
email: jbparkmd@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Kidney Failure, Chronic