<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/NCT03241719</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000590</org_study_id>
    <nct_id>NCT03241719</nct_id>
  </id_info>
  <brief_title>Novel Strategies to Improve Immunomodulation and Non-invasive Clinical Monitoring in VCA</brief_title>
  <official_title>Novel Strategies to Improve Immunomodulation and Non-invasive Clinical Monitoring in Vascularized Composite Allotransplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to develop a feasible and safe regimen for minimization of&#xD;
      immune suppression in recipients of vascularized composite allotransplants (VCA) using a&#xD;
      daily dose of recombinant IL-2. In order to achieve this aim, this trial will:&#xD;
&#xD;
        1. Perform VCA in 5 eligible subjects;&#xD;
&#xD;
        2. Administer recombinant IL-2 at a low-dose to promote the expansion and function of&#xD;
           regulatory T cells in subjects who received VCA; and&#xD;
&#xD;
        3. Minimize immune suppression to tacrolimus single therapy in subjects who received VCA&#xD;
           and recombinant IL-2.&#xD;
&#xD;
      This trial will also investigate if it is possible to predict immune rejection in VCA using&#xD;
      blood and tissue samples from recipients of VCA.&#xD;
&#xD;
      Lastly, this trial will develop non-invasive technologies to monitor for VCA rejection. These&#xD;
      technologies will involve magnetic resonance imaging. Multi-contrast ultra-high resolution MR&#xD;
      imaging (MRI) with serial direct planimetry will be performed in recipients of VCA.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No participants are currently receiving therapy under this protocol, funding is coming to an&#xD;
    end and the PI is leaving the institution.&#xD;
  </why_stopped>
  <start_date type="Actual">October 17, 2017</start_date>
  <completion_date type="Actual">July 21, 2021</completion_date>
  <primary_completion_date type="Actual">July 21, 2021</primary_completion_date>
  <phase>Early Phase 1</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>Number of regulatory T cells</measure>
    <time_frame>4-24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of episodes of rejection</measure>
    <time_frame>1-24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T-cell alloreactivity measured by ELISPOT</measure>
    <time_frame>4-24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steroid dose</measure>
    <time_frame>6-24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mycophenolate dose</measure>
    <time_frame>8-24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Amputation, Traumatic</condition>
  <condition>Amputation;Traumatic;Old</condition>
  <condition>Face Injury</condition>
  <condition>Face; Deformity</condition>
  <condition>Abdominal Wall Defect</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who receive transplantation and undergo IL-2 treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IL-2</intervention_name>
    <description>Subjects will receive vascularized composite allotransplantation (e.g. facial, hand and/or abdominal wall transplants) under conventional immune suppression. No sooner than 3 months after VCA, subjects will receive a protocol of daily recombinant IL-2 at low doses for 8 weeks.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For the VCA portion of the study:&#xD;
&#xD;
          -  Patients referred due to one or more of these conditions: (1) severe facial deformity&#xD;
             comprising more than 25% of the facial area and/or one or more of the central facial&#xD;
             units (i.e. lip(s), nose, eye(s)), (2) single or bilateral upper limb(s) amputation,&#xD;
             where at least one of the limbs was amputated at the level of the wrist or more&#xD;
             proximal, up to the functional shoulder joint, and (3) severe abdominal wall defect&#xD;
             comprising more than 50% of the functional abdominal wall.&#xD;
&#xD;
          -  Injuries must have taken place no more than 15 years and no less than 6 months prior&#xD;
             to presentation for consideration.&#xD;
&#xD;
          -  All other conventional reconstruction approaches will have been either exhausted, or&#xD;
             ruled out due to poor prognosis of outcomes.&#xD;
&#xD;
          -  Patients will need to possess strong motivation and a willingness to commit to&#xD;
             post-transplant rehabilitation.&#xD;
&#xD;
          -  Normal renal and hepatic function within acceptable medical parameters&#xD;
&#xD;
        For the recombinant IL-2 phase of the study:&#xD;
&#xD;
          -  At least 3 months have elapsed since the VCA transplant operation&#xD;
&#xD;
          -  At least 4 weeks on stable immune suppression and steriods (&lt;5 mg QD).&#xD;
&#xD;
          -  No addition or subtraction of other immunosuppressive medications for 4 weeks prior to&#xD;
             enrollment. The dose of immunosuppressive medicines may be adjusted based on the&#xD;
             therapeutic range for that drug.&#xD;
&#xD;
          -  Medical evaluations, clinical and laboratory assessments must deem that participants&#xD;
             have adequate organ function.&#xD;
&#xD;
          -  The effects of some of the study drugs on the developing human fetus are unknown, or&#xD;
             toxic. For this reason, women of child-bearing potential and men must agree to use&#xD;
             adequate contraception (hormonal or barrier method of birth control; abstinence prior&#xD;
             to study entry and for the duration of study participation). Should a women become&#xD;
             pregnant or suspect she is pregnant while participating in this study, she should&#xD;
             inform her treating physician immediately.&#xD;
&#xD;
          -  Subjects must be able to understand and willing to sign a written informed consent&#xD;
             document.&#xD;
&#xD;
          -  Skin biopsies from the transplanted parts must show no evidence of rejection for at&#xD;
             least 3 months prior to study enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For the VCA portion of the study:&#xD;
&#xD;
          -  History of poor compliance with prostheses or rehabilitation&#xD;
&#xD;
          -  Impaired renal, cardiac and/or pulmonary function&#xD;
&#xD;
          -  Compromised ability to understand the risk and benefits of participation in the study&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  Single non-dominant upper limb amputation and no other vascularized composite tissue&#xD;
             injuries justifying VCA&#xD;
&#xD;
        For the IL-2 portion of the study:&#xD;
&#xD;
          -  Active infection&#xD;
&#xD;
          -  Non-healing wounds&#xD;
&#xD;
          -  Pregnancy, because of the potential for teratoenic or abortifacient effects. There is&#xD;
             an unknown but potential risk of adverse events in nursing infants secondary to&#xD;
             treatment of the mother, therefore breastfeeding should be discontinued.&#xD;
&#xD;
          -  Rejection episodes within the past 3 months&#xD;
&#xD;
          -  Concurrent use of calcineurin-inhibitor plus sirolimus&#xD;
&#xD;
          -  New immunosuppressive medication in the 4 weeks prior&#xD;
&#xD;
          -  Post-transplant exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab,&#xD;
             basiliximab, denileukin diftitox) within 100 days prior.&#xD;
&#xD;
          -  Active malignant relapse&#xD;
&#xD;
          -  Donor lymphocyte infusion within 100 days prior&#xD;
&#xD;
          -  Inability to comply with IL-2 treatment regime&#xD;
&#xD;
          -  HIV-positive individuals because of the potential for lethal infections.&#xD;
&#xD;
          -  Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the&#xD;
             principal investigator.&#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>Bohdan Pomahac, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>July 22, 2021</last_update_submitted>
  <last_update_submitted_qc>July 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Bodhan Pomahac</investigator_full_name>
    <investigator_title>Director, Plastic Surgery Transplantation</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amputation, Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03241719
org study id: 2017P000590
nct id: NCT03241719
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to develop a feasible and safe regimen for minimization of
      immune suppression in recipients of vascularized composite allotransplants (VCA) using a
      daily dose of recombinant IL-2. In order to achieve this aim, this trial will:

        1. Perform VCA in 5 eligible subjects;

        2. Administer recombinant IL-2 at a low-dose to promote the expansion and function of
           regulatory T cells in subjects who received VCA; and

        3. Minimize immune suppression to tacrolimus single therapy in subjects who received VCA
           and recombinant IL-2.

      This trial will also investigate if it is possible to predict immune rejection in VCA using
      blood and tissue samples from recipients of VCA.

      Lastly, this trial will develop non-invasive technologies to monitor for VCA rejection. These
      technologies will involve magnetic resonance imaging. Multi-contrast ultra-high resolution MR
      imaging (MRI) with serial direct planimetry will be performed in recipients of VCA.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of regulatory T cells
time frame: 4-24 months
measure: Number of episodes of rejection
time frame: 1-24 months
measure: T-cell alloreactivity measured by ELISPOT
time frame: 4-24 months
measure: Steroid dose
time frame: 6-24 months
measure: Mycophenolate dose
time frame: 8-24 months
arm group label: Treatment
arm group type: Experimental
description: Subjects who receive transplantation and undergo IL-2 treatment
intervention type: Drug
intervention name: IL-2
description: Subjects will receive vascularized composite allotransplantation (e.g. facial, hand and/or abdominal wall transplants) under conventional immune suppression. No sooner than 3 months after VCA, subjects will receive a protocol of daily recombinant IL-2 at low doses for 8 weeks.
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Bohdan Pomahac, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Bodhan Pomahac
investigator title: Director, Plastic Surgery Transplantation
mesh term: Amputation, Traumatic
sharing ipd: No