Novel Strategies to Improve Immunomodulation and Non-invasive Clinical Monitoring in VCA

Description

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.

Study Start Date

October, 17 2017

Estimated Completion Date

December 2019

Interventions

  • Drug: IL-2

Study ID

Brigham and Women's Hospital -- 2017P000590

Status

Recruiting

Trial ID

NCT03241719

Study Type

Interventional

Trial Phase

Early Phase 1

Enrollment Quota

5

Sponsor

Brigham and Women's Hospital

Inclusion Criteria

    For the VCA portion of the study:
  • Patients referred due to one or more of these conditions: (1) severe facial deformity comprising more than 25% of the facial area and/or one or more of the central facial units (i.e. lip(s), nose, eye(s)), (2) single or bilateral upper limb(s) amputation, where at least one of the limbs was amputated at the level of the wrist or more proximal, up to the functional shoulder joint, and (3) severe abdominal wall defect comprising more than 50% of the functional abdominal wall.
  • Injuries must have taken place no more than 15 years and no less than 6 months prior to presentation for consideration.
  • All other conventional reconstruction approaches will have been either exhausted, or ruled out due to poor prognosis of outcomes.
  • Patients will need to possess strong motivation and a willingness to commit to post-transplant rehabilitation.
  • Normal renal and hepatic function as below: ALT ( Alanine aminotransferase) 7-55 U/L AST (Aspartate aminotransferase) 8-48 U/L ALP (Alkaline phosphatase) 45-115 U/L Albumin 3.5-5.0 g/dL Total protein 6.3-7.9 g/dL Bilirubin 0.1-1.0 mg/dL GGT (Gamma glutamyl transpeptidase) 0-30 U/L LDH (Lactate dehydrogenase) 122-222 mcmol/L PT (Prothrombin Time) 10.9-12.5 seconds Blood Urea Nitrogen (BUN) 7-20mg/100ml Serum Creatinine Adult males 0.8
  • 1.4 mg/dl Adult females 0.6 -1.1mg/dl Creatinine Clearance Adult males 97-137 ml/min Adult females 88-128 ml/min Pregnancy May be as high as 150
  • 200 ml/min. For the recombinant IL-2 phase of the study:
  • At least 3 months have elapsed since the VCA transplant operation
  • At least 4 weeks on stable immune suppression of low dose tacrolimus (trough levels ~ 6-8 ng/ml) and mycophenolate (<1000 mg BID mycophenolate mofetil (MMF) or <720 mg BID Myfortic) and prednisone (<5 mg QD).
  • No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range for that drug.
  • Medical evaluations, clinical and laboratory assessments must deem that participants have adequate organ function.
  • The effects of some of the study drugs on the developing human fetus are unknown, or toxic. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control
  • abstinence prior to study entry and for the duration of study participation). Should a women become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Subjects must be able to understand and willing to sign a written informed consent document.
  • Skin biopsies from the transplanted parts must show no evidence of rejection for at least 3 months prior to study enrollment.

Exclusion Criteria

    For the VCA portion of the study:
  • History of poor compliance with prostheses or rehabilitation
  • Impaired renal, cardiac and/or pulmonary function
  • Compromised ability to understand the risk and benefits of participation in the study
  • Active malignancy
  • Single non-dominant upper limb amputation and no other vascularized composite tissue injuries justifying VCA For the IL-2 portion of the study:
  • Active infection
  • Non-healing wounds
  • Pregnancy, because of the potential for teratoenic or abortifacient effects. There is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, therefore breastfeeding should be discontinued.
  • Rejection episodes within the past 3 months
  • Concurrent use of calcineurin-inhibitor plus sirolimus
  • New immunosuppressive medication in the 4 weeks prior
  • Post-transplant exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior.
  • Active malignant relapse
  • Donor lymphocyte infusion within 100 days prior
  • Inability to comply with IL-2 treatment regime
  • HIV-positive individuals because of the potential for lethal infections.
  • Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the principal investigator.

Gender

All

Ages

18 Years to 60 Years

Accepts Healthy Volunteers

No

Study Locations and Contact Information (4)

Study Location Distance Name Phone Email
Brigham and Womens Hospital - Boston, Massachusetts 2.6 miles Ashley Tremblay 617-732-7796 atremblay1@bwh.harvard.edu
Brigham and Womens Hospital - Boston, Massachusetts 2.6 miles Ashley Tremblay 617-732-7796 atremblay1@bwh.harvard.edu
Brigham and Womens Hospital - Boston, Massachusetts 2.6 miles Ashley Tremblay 617-732-7796 atremblay1@bwh.harvard.edu
Brigham and Womens Hospital - Boston, Massachusetts 2.6 miles Ashley Tremblay 617-732-7796 atremblay1@bwh.harvard.edu

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