Human Upper Extremity Allotransplantation

NCT01459107 | Recruiting Phase 2 DMC

• 1 other identifier: NA_00046418
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Millions of people each year sustain injuries, have tumors surgically removed, or are born with defects that require complex reconstructive surgeries to repair. In the case of hand, forearm, or arm amputation, prostheses only provide less than optimal motor function and no sensory feedback. However, hand and arm transplantation is a means to restore the appearance, anatomy, and function of a native hand. Although over 70 hand transplants have been performed to date and good functional results have been achieved, widespread clinical use has been limited due to 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 hand 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 hand transplantation as a safe and effective reconstructive treatment for upper extremity amputations by minimizing maintenance immunosuppression therapy in unilateral and bilateral hand/forearm 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 30 human hand transplants employing this novel protocol. Specific Aims: 1) To establish hand transplantation as a safe and effective reconstructive strategy for the treatment of upper extremity amputations; 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: Hand transplantation could help upper extremity amputees recover functionality, self-esteem, and the capability to reintegrate into family and social life as "whole" individuals. The 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 widespread clinical application of hand transplantation.

Conditions

Amputation, Traumatic; Wounds and Injuries; Hand Injuries

Keywords

Hand Transplant; Composite Tissue Allotransplantation (CTA); Vascularized Composite Allotransplantation (VCA); Composite Tissue; Amputation; Upper limb; Immunosuppression

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

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

Procedure: Deceased donor hand transplantation; Drug: Bone marrow cell-based therapy & single-drug immunosuppression.

Interventions

Deceased donor hand transplantation PROCEDURE

Deceased donor hand is surgically attached to recipient arm's stump.

Treatment (Transplantation)

Bone marrow cell-based therapy & single-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 upper extremities 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.

Treatment (Transplantation)

Eligibility Criteria

• Age: 18 Years - 69 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) unilateral or bilateral upper limb loss (below the shoulder) desiring limb transplantation.
• Below-shoulder amputation.
• Functionless or minimally functional hand desiring removal of functionless / minimally functional hand followed by transplantation.
• Male or female and of any race, color or ethnicity.
• Aged 18-69 years.
• Completes the protocol informed consent form.

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 bone marrow infusion as part of the treatment regime.
• USA citizen or equivalent, or foreigner with documentation of ability to pay for transplant and required follow-up care.
• Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.
• Donors will be selected by the upper extremity transplant team in conjunction with the organ procurement organization (OPO) according to the following criteria:
• Brain dead meeting the criteria for Determination of Death.
• Family consent for limb donation.
• Stable donor (i.e., does not require excessive vasopressors to maintain blood pressure).
• Aged 16 - 65 years.
• Limb matched for size with recipient.

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

Related Links

• Study website including additional related information.

MeSH Terms

Conditions

Amputation, Traumatic; Wounds and Injuries; Hand Injuries

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: September 29, 2011
• First Posted: October 25, 2011
• Study Start: July 21, 2011
• Primary Completion (Estimated): June 30, 2036
• Study Completion (Estimated): June 30, 2036
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)