<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/NCT02244801</url>
  </required_header>
  <id_info>
    <org_study_id>ONEdarTreg14</org_study_id>
    <nct_id>NCT02244801</nct_id>
  </id_info>
  <brief_title>Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Renal Transplantation (The ONE Study )</brief_title>
  <acronym>DART</acronym>
  <official_title>Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Renal Transplantation: A ONE Study Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Seventh Framework Programme</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase I pilot study will evaluate the safety, and tolerability of darTreg infusion for&#xD;
      adult, de novo, living donor renal transplant recipients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A single-center, open-label, dose-escalation pilot trial of a single infusion of darTregs in&#xD;
      two dosing cohorts. This study is an independent single-center clinical trial. However, the&#xD;
      organizational and mechanistic infrastructure of the study will be provided by the ONE Study&#xD;
      project, a European Union funded collaborative project, whose objective is to assess distinct&#xD;
      purified hematopoietic immunoregulatory cells as clinical therapies in solid organ&#xD;
      transplantation. This study is one of multiple clinical trials within the framework of The&#xD;
      ONE Study project, based on the same general design.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2015</start_date>
  <completion_date type="Actual">August 28, 2018</completion_date>
  <primary_completion_date type="Actual">September 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of biopsy-confirmed acute rejection (BCAR) following renal transplantation.</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
    <description>Explore the immunomodulatory potential, safety and tolerability of a single infusion of darTregs as adjunct immunosuppressive treatment through the incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks following renal transplantation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first acute rejection episode</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of acute rejection episodes</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
    <description>severity of acute rejection episodes based on response to treatment and histological scoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total immunosuppressive burden at 60 weeks post-transplantation</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
    <description>Total immunosuppressive burden assessed at last study visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevention of chronic graft dysfunction (chronic rejection or IF/TA)</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
    <description>chronic graft dysfunction assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Avoidance of drug-related complications by immunosuppressant reduction</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
    <description>Assessed by the incidence of reported adverse drug reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical disturbances caused by cell infusion</measure>
    <time_frame>1 week</time_frame>
    <description>Assessed by Incidence of acute toxicities associated with infusion of the cell product</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections especially CMV (cytomegalovirus ), EBV (Epstein-Barr virus) and polyoma virus</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of neoplasia</measure>
    <time_frame>60 weeks post renal transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of patients treated for subclinical acute rejection</measure>
    <time_frame>60 weeks post transplantation</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of malignancies arising directly from darTreg infusion</measure>
    <time_frame>60 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>incidence of autoimmune disorders</measure>
    <time_frame>60 weeks post transplantation</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>A Health-Economics Subproject will evaluate the health-related qualify-of-life of trail patients using patient-reported outcome measures</measure>
    <time_frame>60 weeks post transplantation</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>3 subjects treated with a target dose of 300 million darTreg with the possibility of expanding to 5 patients if safety signals should require additional patients be observed at the 300 million dose.&#xD;
The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The second cohort will comprise a minimum of 3 and up to 5 subjects treated at a target dose of 900 million darTreg, depending on how many patients were required to be treated in lower dose group.&#xD;
The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>darTreg infusion</intervention_name>
    <description>The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients. sBc production for darTreg manufacturing for the second subject in each cohort may be initiated but the second subject may not undergo leukapheresis until the safety review is complete.&#xD;
Once the last subject in the first cohort reaches week 4 post-infusion, the DSMB will conduct a thorough review of all available data to make a determination about proceeding with additional patients at the lower dose or proceeding to the second dosing cohort. sBc production for darTreg manufacturing for the subsequent subject may be initiated but the patient may not undergo leukapheresis until the DSMB( Data Safety and Monitoring Board ) has approved enrollment of subsequent subjects.</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <other_name>darTregs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: (organ donor eligibility)&#xD;
&#xD;
          1. Eligible for live kidney donation&#xD;
&#xD;
          2. At least 18 years of age&#xD;
&#xD;
          3. An ABO blood type compatible with the organ recipient&#xD;
&#xD;
          4. Willing and able to provide a blood sample for The ONE Study IM (Immune Monitoring)&#xD;
             Subproject&#xD;
&#xD;
          5. Willing to provide personal and medical/biological data for the trial analysis&#xD;
&#xD;
          6. Eligible to give blood for B cell source prior to organ donation&#xD;
&#xD;
          7. Signed and dated written informed consent*. *For subjects unable to read and/or write,&#xD;
             oral informed consent observed by an independent witness is acceptable if the subject&#xD;
             has fully understood oral information given by the Investigator. The witness should&#xD;
             sign the consent form on behalf of the subject.&#xD;
&#xD;
        In signing the donor information sheet/informed consent form (DIS/ICF), organ donors agree&#xD;
        to undergo phlebotomy to provide donor B cells for the production of darTreg, to provide a&#xD;
        blood sample for the IM Subproject, and permit access to their medical records for the&#xD;
        collection of specified demographic and medical/biological data for the trial.&#xD;
&#xD;
        Organ Recipient eligibility:&#xD;
&#xD;
        A prospective kidney transplant recipient is eligible for enrollment into the study if all&#xD;
        of the following inclusion criteria apply:&#xD;
&#xD;
          1. Chronic renal insufficiency necessitating kidney transplantation and approved to&#xD;
             receive a primary kidney allograft from a living donor&#xD;
&#xD;
          2. At least 18 years of age&#xD;
&#xD;
          3. Able to commence the immunosuppressive regimen at the protocol-specified time point&#xD;
&#xD;
          4. Willing and able to participate in The ONE Study IM and HEC (Health-Economics&#xD;
             Subproject) subprojects&#xD;
&#xD;
          5. Adequate venous access to support leukapheresis&#xD;
&#xD;
          6. Signed and dated written informed consent*.&#xD;
&#xD;
               -  For patients unable to read and/or write, oral informed consent observed by an&#xD;
                  independent witness is acceptable if the patient has fully understood oral&#xD;
                  information given by the Investigator. The witness should sign the consent form&#xD;
                  on behalf of the patient.&#xD;
&#xD;
        Exclusion Criteria: (organ donor)&#xD;
&#xD;
        If a prospective donor fulfills any of the following criteria, they are ineligible for the&#xD;
        trial:&#xD;
&#xD;
          1. Genetically identical to the prospective organ recipient at the HLA (human leukocyte&#xD;
             antigen) loci (0-0-0 mismatch)&#xD;
&#xD;
          2. CMV-positive and donating to a CMV-negative recipient&#xD;
&#xD;
          3. Exposure to any investigational agents at the time of kidney donation, or within 28&#xD;
             days prior to kidney donation&#xD;
&#xD;
          4. Any form of substance abuse, psychiatric disorder, or other condition that, in the&#xD;
             opinion of the Investigator, may invalidate communication with the Investigator and/or&#xD;
             designated study personnel&#xD;
&#xD;
          5. Subjects unable to freely give their informed consent (e.g. individuals under legal&#xD;
             guardianship).&#xD;
&#xD;
        Exclusion criteria (organ recipient)&#xD;
&#xD;
          1. Patient has previously received any tissue or organ transplant other than the planned&#xD;
             kidney graft&#xD;
&#xD;
          2. Known contraindication to the protocol-specified treatments / medications&#xD;
&#xD;
          3. Genetically identical to the prospective organ donor at the HLA (human leukocyte&#xD;
             antigen) loci (0-0-0 mismatch)&#xD;
&#xD;
          4. PRA (panel reactive antibody) grade &gt; 40% within 6 months prior to enrollment&#xD;
&#xD;
          5. Previous treatment with any desensitization procedure (with or without IVIg)&#xD;
&#xD;
          6. Concomitant malignancy or history of malignancy within 5 years prior to planned study&#xD;
             entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of&#xD;
             the skin)&#xD;
&#xD;
          7. Evidence of significant local or systemic infection&#xD;
&#xD;
          8. HIV-positive, EBV-negative or suffering chronic viral hepatitis&#xD;
&#xD;
          9. CMV-negative and receiving a kidney from a CMV-positive donor&#xD;
&#xD;
         10. Significant liver disease, defined as persistently elevated AST (aspartate&#xD;
             aminotransferase) and/or ALT(alanine aminotransferase) levels &gt; 2 x ULN (Upper Limit&#xD;
             of Normal range)&#xD;
&#xD;
         11. Malignant or pre-malignant hematological conditions&#xD;
&#xD;
         12. Neutrophils &lt; 1000/μl ; platelets &lt; 100,000/μl&#xD;
&#xD;
         13. Regulatory T cells present in peripheral blood at &lt;30/µL&#xD;
&#xD;
         14. Any uncontrolled medical condition or concurrent disease that could interfere with the&#xD;
             study objectives&#xD;
&#xD;
         15. Any condition which, in the judgment of the Investigator, would place the subject at&#xD;
             undue risk&#xD;
&#xD;
         16. Ongoing treatment with systemic immunosuppressive drugs at study entry&#xD;
&#xD;
         17. Patients who have received anti-T cell therapy within 30 days prior to transplant&#xD;
             surgery&#xD;
&#xD;
         18. Participation in another clinical trial during the study or within 28 days prior to&#xD;
             planned study entry&#xD;
&#xD;
         19. Female patients of reproductive potential with a positive pregnancy test at enrollment&#xD;
&#xD;
         20. Female patients who are breast-feeding&#xD;
&#xD;
         21. All female patients of reproductive potential* UNLESS the patient is willing to use an&#xD;
             acceptable birth control for the duration of the study unless the patient chooses&#xD;
             abstinence (she chooses to avoid heterosexual intercourse completely) (See Table 2.&#xD;
             Acceptable Contraception Methods for Females of Reproductive Potential)&#xD;
&#xD;
         22. Male patients unwilling to use a reliable and effective form of contraception for 3&#xD;
             months after darTreg dosing&#xD;
&#xD;
         23. Psychological, familial, sociological or geographical factors potentially hampering&#xD;
             compliance with the study protocol and follow-up visit schedule&#xD;
&#xD;
         24. Any form of substance abuse, psychiatric disorder, or other condition that, in the&#xD;
             opinion of the Investigator, may invalidate communication with the Investigator and/or&#xD;
             designated study personnel&#xD;
&#xD;
         25. Patients unable to freely give their informed consent (e.g. individuals under legal&#xD;
             guardianship).&#xD;
&#xD;
               -  Females of reproductive potential include girls who have entered puberty and all&#xD;
                  women who have a uterus and have not passed through menopause. Menopause is the&#xD;
                  permanent end of menstruation and fertility. Menopause should be clinically&#xD;
                  confirmed by a patient's healthcare practitioner. Some commonly used diagnostic&#xD;
                  criteria include 1) 12 months of spontaneous amenorrhea (not amenorrhea induced&#xD;
                  by a medical condition or medical therapy) or 2) postsurgical from a bilateral&#xD;
                  oophorectomy.&#xD;
&#xD;
        Exclusion Criteria B (organ recipient)&#xD;
&#xD;
        Below are exclusion criteria to be assessed post-transplantation and prior to darTreg&#xD;
        infusion. Subjects who meet any of these criteria should not receive a darTreg-infusion:&#xD;
&#xD;
          1. Unacceptable darTreg product.&#xD;
&#xD;
          2. Delayed graft function (requiring dialysis post-transplant).&#xD;
&#xD;
          3. Requiring oxygen supplementation to keep capillary oxygen saturations &gt;95%.&#xD;
&#xD;
          4. Any medical or technical complications (e.g. myocardial infarction, urine leak, wound&#xD;
             dehiscence, pneumonia, ongoing fevers, etc.) that in the judgment of the investigators&#xD;
             or responsible clinician would put the subject at undue risk.-&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sang-Mo Kang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California San Francisco - Transplant Department. 513 Parnassus Ave HSE 504</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>ICH Harmonised Tripartite Guideline. Statistical principles for clinical trials. International Conference on Harmonisation E9 Expert Working Group. Stat Med. 1999 Aug 15;18(15):1905-42. No abstract available.</citation>
    <PMID>10532877</PMID>
  </reference>
  <reference>
    <citation>Francillon A, Pickering G, Belorgey C. Exploratory clinical trials: implementation modes &amp; guidelines, scope and regulatory framework. Therapie. 2009 May-Jun;64(3):149-59. doi: 10.2515/therapie/2009022. Epub 2009 Aug 13. English, French.</citation>
    <PMID>19671427</PMID>
  </reference>
  <reference>
    <citation>Morris PJ. Transplantation--a medical miracle of the 20th century. N Engl J Med. 2004 Dec 23;351(26):2678-80. doi: 10.1056/NEJMp048256. No abstract available.</citation>
    <PMID>15616201</PMID>
  </reference>
  <reference>
    <citation>Sayegh MH, Carpenter CB. Transplantation 50 years later--progress, challenges, and promises. N Engl J Med. 2004 Dec 23;351(26):2761-6. doi: 10.1056/NEJMon043418. No abstract available.</citation>
    <PMID>15616214</PMID>
  </reference>
  <reference>
    <citation>Gibson T, Medawar PB. The fate of skin homografts in man. J Anat. 1943 Jul;77(Pt 4):299-310.4. No abstract available.</citation>
    <PMID>17104936</PMID>
  </reference>
  <reference>
    <citation>Medawar PB. The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council. J Anat. 1944 Oct;78(Pt 5):176-99. No abstract available.</citation>
    <PMID>17104960</PMID>
  </reference>
  <reference>
    <citation>Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004 Dec 23;351(26):2715-29. doi: 10.1056/NEJMra033540. No abstract available. Erratum In: N Engl J Med. 2005 Mar 10;352(10):1056.</citation>
    <PMID>15616206</PMID>
  </reference>
  <results_reference>
    <citation>MERRILL JP, MURRAY JE, HARRISON JH, GUILD WR. Successful homotransplantation of the human kidney between identical twins. J Am Med Assoc. 1956 Jan 28;160(4):277-82. doi: 10.1001/jama.1956.02960390027008. No abstract available.</citation>
    <PMID>13278189</PMID>
  </results_reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>October 10, 2018</last_update_submitted>
  <last_update_submitted_qc>October 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Sang-Mo Kang</investigator_full_name>
    <investigator_title>Associate Professor of Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney 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/NCT02244801
org study id: ONEdarTreg14
nct id: NCT02244801
lead sponsor: 
collaborator: 
has dmc: Yes
This Phase I pilot study will evaluate the safety, and tolerability of darTreg infusion for
      adult, de novo, living donor renal transplant recipients.
A single-center, open-label, dose-escalation pilot trial of a single infusion of darTregs in
      two dosing cohorts. This study is an independent single-center clinical trial. However, the
      organizational and mechanistic infrastructure of the study will be provided by the ONE Study
      project, a European Union funded collaborative project, whose objective is to assess distinct
      purified hematopoietic immunoregulatory cells as clinical therapies in solid organ
      transplantation. This study is one of multiple clinical trials within the framework of The
      ONE Study project, based on the same general design.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of biopsy-confirmed acute rejection (BCAR) following renal transplantation.
time frame: 60 weeks post renal transplantation
description: Explore the immunomodulatory potential, safety and tolerability of a single infusion of darTregs as adjunct immunosuppressive treatment through the incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks following renal transplantation.
measure: Time to first acute rejection episode
time frame: 60 weeks post renal transplantation
measure: Severity of acute rejection episodes
time frame: 60 weeks post renal transplantation
description: severity of acute rejection episodes based on response to treatment and histological scoring
measure: Total immunosuppressive burden at 60 weeks post-transplantation
time frame: 60 weeks post renal transplantation
description: Total immunosuppressive burden assessed at last study visit
measure: Prevention of chronic graft dysfunction (chronic rejection or IF/TA)
time frame: 60 weeks post renal transplantation
description: chronic graft dysfunction assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures
measure: Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection
time frame: 60 weeks post renal transplantation
measure: Avoidance of drug-related complications by immunosuppressant reduction
time frame: 60 weeks post renal transplantation
description: Assessed by the incidence of reported adverse drug reactions
measure: Biochemical disturbances caused by cell infusion
time frame: 1 week
description: Assessed by Incidence of acute toxicities associated with infusion of the cell product
measure: Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections especially CMV (cytomegalovirus ), EBV (Epstein-Barr virus) and polyoma virus
time frame: 60 weeks post renal transplantation
measure: Incidence of neoplasia
time frame: 60 weeks post renal transplantation
measure: Incidence of patients treated for subclinical acute rejection
time frame: 60 weeks post transplantation
measure: Incidence of malignancies arising directly from darTreg infusion
time frame: 60 weeks
measure: incidence of autoimmune disorders
time frame: 60 weeks post transplantation
measure: A Health-Economics Subproject will evaluate the health-related qualify-of-life of trail patients using patient-reported outcome measures
time frame: 60 weeks post transplantation
arm group label: Cohort 1
arm group type: Other
description: 3 subjects treated with a target dose of 300 million darTreg with the possibility of expanding to 5 patients if safety signals should require additional patients be observed at the 300 million dose.
The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients.
arm group label: Cohort 2
arm group type: Other
description: The second cohort will comprise a minimum of 3 and up to 5 subjects treated at a target dose of 900 million darTreg, depending on how many patients were required to be treated in lower dose group.
The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients.
intervention type: Drug
intervention name: darTreg infusion
description: The first subject in each dosing cohort will be monitored for 4 weeks after darTreg infusion. Following the 4 week observation period, the study team will conduct a thorough review of all available data to ensure that there are no safety signals and to make a determination about proceeding with additional patients. sBc production for darTreg manufacturing for the second subject in each cohort may be initiated but the second subject may not undergo leukapheresis until the safety review is complete.
Once the last subject in the first cohort reaches week 4 post-infusion, the DSMB will conduct a thorough review of all available data to make a determination about proceeding with additional patients at the lower dose or proceeding to the second dosing cohort. sBc production for darTreg manufacturing for the subsequent subject may be initiated but the patient may not undergo leukapheresis until the DSMB( Data Safety and Monitoring Board ) has approved enrollment of subsequent subjects.
arm group label: Cohort 1
arm group label: Cohort 2
other name: darTregs
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Sang-Mo Kang, M.D.
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
citation: ICH Harmonised Tripartite Guideline. Statistical principles for clinical trials. International Conference on Harmonisation E9 Expert Working Group. Stat Med. 1999 Aug 15;18(15):1905-42. No abstract available.
PMID: 10532877
citation: Francillon A, Pickering G, Belorgey C. Exploratory clinical trials: implementation modes & guidelines, scope and regulatory framework. Therapie. 2009 May-Jun;64(3):149-59. doi: 10.2515/therapie/2009022. Epub 2009 Aug 13. English, French.
PMID: 19671427
citation: Morris PJ. Transplantation--a medical miracle of the 20th century. N Engl J Med. 2004 Dec 23;351(26):2678-80. doi: 10.1056/NEJMp048256. No abstract available.
PMID: 15616201
citation: Sayegh MH, Carpenter CB. Transplantation 50 years later--progress, challenges, and promises. N Engl J Med. 2004 Dec 23;351(26):2761-6. doi: 10.1056/NEJMon043418. No abstract available.
PMID: 15616214
citation: Gibson T, Medawar PB. The fate of skin homografts in man. J Anat. 1943 Jul;77(Pt 4):299-310.4. No abstract available.
PMID: 17104936
citation: Medawar PB. The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council. J Anat. 1944 Oct;78(Pt 5):176-99. No abstract available.
PMID: 17104960
citation: Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004 Dec 23;351(26):2715-29. doi: 10.1056/NEJMra033540. No abstract available. Erratum In: N Engl J Med. 2005 Mar 10;352(10):1056.
PMID: 15616206
citation: MERRILL JP, MURRAY JE, HARRISON JH, GUILD WR. Successful homotransplantation of the human kidney between identical twins. J Am Med Assoc. 1956 Jan 28;160(4):277-82. doi: 10.1001/jama.1956.02960390027008. No abstract available.
PMID: 13278189
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Sang-Mo Kang
investigator title: Associate Professor of Surgery
mesh term: Kidney Diseases