Human Upper Extremity Allotransplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Johns Hopkins University
Sponsor:
Collaborators:
ARMED FORCES INSTITUTE OF REGENERATIVE MEDICINE (AFIRM)
US Army Medical Research Acquisition Activity (USAMRAA)
Information provided by (Responsible Party):
W. P. Andrew Lee, M.D., Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01459107
First received: September 29, 2011
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Amputation, Traumatic
Wounds and Injuries
Hand Injuries
Procedure: Deceased donor hand transplantation
Drug: Bone marrow cell-based therapy & single-drug immunosuppression.
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Human Upper Extremity Allotransplantation

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Graft Survival [ Time Frame: Transplantation through end of study period (up to 5 years) ] [ Designated as safety issue: No ]
    Post-operative graft survival will be documented monthly Months 1-12 and quarterly (every 3 months) Years 2-5.


Secondary Outcome Measures:
  • Documentation of immunosuppression required by transplanted participants to maintain graft. [ Time Frame: Transplantation to end of study period (up to 5 years) ] [ Designated as safety issue: No ]
    Post-operative serum trough levels will be documented daily Days 1-28, semiweekly Weeks 5-12, weekly Weeks 13-25, biweekly Weeks 26-38, monthly Months 10-12, and quarterly (every 3 months) Years 2-5.


Estimated Enrollment: 30
Study Start Date: July 2011
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Transplantation)
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
Deceased donor hand is surgically attached to recipient arm's stump.
Drug: Bone marrow cell-based therapy & single-drug immunosuppression.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recent (≥6 months) or remote (i.e., several decades) unilateral or bilateral upper limb loss (below the shoulder) desiring limb transplantation.
  • Below-shoulder amputation.
  • Male or female and of any race, color or ethnicity.
  • Aged 18-69 years.
  • Completes the protocol informed consent form.
  • No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (see Donor and Recipient Exclusion Criteria below. If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of upper extremity transplantation.)
  • 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.
  • Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.

Exclusion Criteria:

  • Positive for any of the following conditions:

    • Untreated sepsis.
    • HIV (active or seropositive).
    • Active tuberculosis.
    • Hepatitis B or C.
    • Viral encephalitis.
    • Toxoplasmosis.
    • Malignancy (within past 5 years).
    • Current/recent (within 3 months of donation/screening consent) IV drug abuse.
    • Paralysis of ischemic or traumatic origin.
    • Inherited peripheral neuropathy.
    • Infectious, post infectious, or inflammatory (axonal or demyelinating) neuropathy.
    • Toxic neuropathy (i.e. heavy metal poisoning, drug toxicity, industrial agent exposure).
    • Mixed connective tissue disease.
    • Severe deforming rheumatoid or osteoarthritis in the limb.
  • Conditions that, in the opinion of the study team, may impact the immunomodulatory protocol potentially exposing the recipient to an unacceptable risk under immunosuppressive treatment.
  • Sensitized recipients with high levels (50%) of panel-reactive HLA antibodies.
  • Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thalassemias, Sickle Cell disease, etc.
  • Mixed connective tissue diseases and collagen diseases can result in poor wound healing after surgery.
  • Conditions that may impact functional outcomes including Lipopolysaccharidosis and amyloidosis (may impact nerve regeneration) or rare disorders of bone healing like osteopetrosis.
  • Patients considered unsuitable per the consulted Psychiatrists appraisal.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459107

Contacts
Contact: Cynthia Cohen, DNP,RN,CRNP 410-502-3895 ccohen3@jhmi.edu

Locations
United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21287
Contact: Carisa M Cooney, MPH, CCRP    443-287-4629    ccooney3@jhmi.edu   
Principal Investigator: W. P. Andrew Lee, MD         
Sub-Investigator: Gerald Brandacher, MD         
Sub-Investigator: Stefan Schneeberger, MD         
Sub-Investigator: Damon S Cooney, MD, PhD         
Sub-Investigator: Justin Sacks, MD         
Sponsors and Collaborators
Johns Hopkins University
ARMED FORCES INSTITUTE OF REGENERATIVE MEDICINE (AFIRM)
US Army Medical Research Acquisition Activity (USAMRAA)
Investigators
Principal Investigator: W. P. Andrew Lee, MD Johns Hopkins University
  More Information

Additional Information:
Publications:
Responsible Party: W. P. Andrew Lee, M.D., Professor and Chairman, Department of Plastic and Reconstructive Surgery, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01459107     History of Changes
Other Study ID Numbers: NA_00046418
Study First Received: September 29, 2011
Last Updated: June 27, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Hand Transplant
CTA
VCA
Composite Tissue
Amputation
Upper limb
Immunosuppression

Additional relevant MeSH terms:
Amputation, Traumatic
Hand Injuries
Wounds and Injuries

ClinicalTrials.gov processed this record on July 28, 2014