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

NCT03241719 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 2017P000590
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Perform VCA in 5 eligible subjects;
2. 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. 3.Minimize immune suppression to tacrolimus single therapy in subjects who received VCA and recombinant IL-2.

Conditions

Amputation, Traumatic; Amputation;Traumatic;Old; Face Injury; Face; Deformity; Abdominal Wall Defect

Outcome Measures

Primary Outcomes (1)

• Number of regulatory T cells

  4-24 months

Secondary Outcomes (4)

• Number of episodes of rejection

  1-24 months

• T-cell alloreactivity measured by ELISPOT

  4-24 months

• Steroid dose

  6-24 months

• Mycophenolate dose

  8-24 months

Study Arms (1)

Treatment

EXPERIMENTAL

Subjects who receive transplantation and undergo IL-2 treatment

Drug: IL-2

Interventions

IL-2 DRUG

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.

Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 within acceptable medical parameters
• 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 and steriods (\<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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Amputation, Traumatic; Facial Injuries; Facies; Congenital Abnormalities

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Bohdan Pomahac, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Plastic Surgery Transplantation

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 7, 2017
• Study Start: October 17, 2017
• Primary Completion: July 21, 2021
• Study Completion: July 21, 2021
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)