Human Craniomaxillofacial Allotransplantation

NCT01889381 | Recruiting Phase 2 DMC

• 1 other identifier: NA_00067257
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The human face is critically important for breathing, eating, seeing, and speaking/ communicating, but its most important job may be to look like a human face. Devastating facial deformities often cause affected individuals to avoid human contact and disappear from society. Although current surgical advancements can somewhat restore facial defects, this process often requires many operations and the resulting face only resembles the human face. To date, over 20 face transplants have been performed with highly encouraging functional and aesthetic results, but widespread clinical use has been limited due to the adverse effects of life-long and high-dose immunosuppression needed to prevent graft rejection. Risks include infection, cancer, and metabolic problems, all of which can greatly affect recipients' quality of life, make the procedure riskier, and jeopardize the potential benefits of face transplantation. Study Design: This non-randomized, Phase II clinical trial will document the use of a new immunomodulatory protocol (aka - Pittsburgh Protocol, Starzl Protocol) for establishing face transplantation as a safe and effective reconstructive treatment for devastating injuries/ defects by minimizing maintenance immunosuppression therapy in face transplant patients. This protocol combines lymphocyte depletion with donor bone marrow cell infusion and has enabled graft survival using low doses of a single immunosuppressive drug followed by weaning of treatment. Initially designed for living-related solid organ donation, this regimen has been adapted for use with grafts donated by deceased donors. The investigators propose to perform 15 full or partial human face transplants employing this novel protocol. Specific Aims: 1) To establish face transplantation as a safe and effective reconstructive strategy for the treatment of devastating facial injuries/defects; 2) To reduce the risk of rejection and enable allograft survival while minimizing the requirement for long-term, high-dose, multi-drug immunosuppression. Significance of Research: Face transplantation could help injured individuals recover functionality, self-esteem, and the ability to reintegrate into family and social life as "whole" individuals. This protocol offers the potential for minimizing the morbidity of maintenance immunosuppression, thereby beneficially shifting the risk/benefit ratio of this life-enhancing procedure and enabling a wider clinical application of face transplantation.

Conditions

Facial Injuries; Traumatic Wounds and Injuries; Craniofacial Injuries; Craniofacial Defects; Facial Transplantation; Facial Deformity

Keywords

Facial Injuries; Face Transplant; Facial Transplantation; Facial Deformity

Outcome Measures

Primary Outcomes (1)

• Graft Survival

  Post-operative graft survival will be documented monthly Months 1-12 and quarterly (every 3 months) Years 2-5.

  Transplantation through end of study period (up to 5 years)

Secondary Outcomes (1)

• Documentation of immunosuppression required by transplanted participants to maintain graft.

  Transplantation to end of study period (up to 5 years)

Study Arms (1)

Treatment (Transplantation)

EXPERIMENTAL

Face transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning.

Drug: Bone marrow cell-based therapy & 1-drug immunosuppression.

Interventions

Bone marrow cell-based therapy & 1-drug immunosuppression. DRUG

This protocol uses a novel bone marrow cell-based therapy for composite tissue allotransplantation (CTA) rather than conventional triple-drug immunosuppression to facilitate long-term graft survival of deceased donor human faces under low-dose maintenance immunosuppression. Initial T-cell depletion with alemtuzumab is followed by upper extremity transplantation and tacrolimus maintenance therapy. Donor bone marrow cells are infused on Day 10 (±4 days) post-transplantation to elicit a host alloimmune response triggering exhaustion and deletion of the respective host (anti-donor) lymphocyte clones. Subsequently, tacrolimus therapy is given for at least 6 months before spaced weaning is considered in stable recipients.

Also known as: Deceased donor face transplantation

Treatment (Transplantation)

Eligibility Criteria

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

You may qualify if:

• Recent (≥6 months) or remote (i.e., several decades) craniomaxillofacial injury
• Male or female and of any race, color, or ethnicity.
• Aged 18-65 years.
• Strong desire to undergo craniomaxillofacial transplantation.
• Completes the protocol informed consent form.
• Non-smoker, defined by having never smoked or having quit \>6 consecutive months prior to screening.

You may not qualify if:

• No co-existing psycho-social problems (i.e., alcoholism, drug abuse).
• Negative for malignancy for past 5 years.
• Negative for HIV at transplant.
• Negative crossmatch with donor.
• If female of child-bearing potential, negative serum pregnancy test.
• If female of child-bearing potential, consent to use reliable contraception for at least one year following transplantation.
• Consents to cell collection, storage, and bone marrow infusion as part of the treatment regime.
• USA citizen or equivalent.
• Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.
• Positive for any of the following conditions:
• Untreated sepsis.
• HIV (active or seropositive).
• Active tuberculosis.
• Active Hepatitis B infection.
• Hepatitis C.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

RECRUITING

Related Publications (1)

• Schneeberger S, Gorantla VS, Brandacher G, Zeevi A, Demetris AJ, Lunz JG, Metes DM, Donnenberg AD, Shores JT, Dimartini AF, Kiss JE, Imbriglia JE, Azari K, Goitz RJ, Manders EK, Nguyen VT, Cooney DS, Wachtman GS, Keith JD, Fletcher DR, Macedo C, Planinsic R, Losee JE, Shapiro R, Starzl TE, Lee WP. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013 Feb;257(2):345-51. doi: 10.1097/SLA.0b013e31826d90bb.

  PMID: 23001085 BACKGROUND

MeSH Terms

Conditions

Facial Injuries; Wounds and Injuries

Condition Hierarchy (Ancestors)

Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases

Study Officials

• Damon Cooney, MD, PHD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jane Littleton, CRNP, MSN

CONTACT

410-955-6875; jlittl38@jhmi.edu

TBD TBD

CONTACT

443-287-7848

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: June 28, 2013
• Study Start: August 1, 2012
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2031
• Last Updated: August 14, 2025

Record last verified: 2025-08

Locations

US (1)