Allogeneic Skin Grafting

Allogeneic Skin Grafting in the Treatment of Chronic Cutaneous Graft-versus-host Disease: a Pilot Study

The primary study objective is to evaluate local response to split-thickness skin grafts from a matched bone marrow donor to chronic GVHD-affected skin in a hematopoietic stem cell transplant patient.

Study Overview

• Status: Withdrawn
• Conditions: GVHD
• Intervention / Treatment: Device: CelluTome® Epidermal Harvesting System

Detailed Description

While the mechanisms are still under active study, GVHD is thought to be a donor T-cell mediated attack that preferentially targets three organs: skin, intestine, and liver. T lymphocytes from the donor identify the patient's organ tissues as foreign and initiate inflammation, leading to end organ damage. The investigator's traditional approach has been to use immune suppressing drugs to dampen this inflammatory response after transplantation. However, this approach is ultimately ineffective for a significant percentage of patients. Therefore, the primary objective of this proposal is to test a novel non-immunosuppressive approach to treatment of cutaneous GVHD using allogeneic skin grafting in an effort to tolerize the engrafted immune system to skin it previously recognized as foreign. The potential benefit to transplant patients is tremendous, including reduced immunosuppression, improved quality of life and lower mortality.

A potential novel approach is to apply split-thickness skin grafts from the bone marrow donor to the affected patient's skin. There are four existing case reports that have shown positive outcomes in wound healing in chronic GVHD-associated ulcers. In all four cases, skin grafts were harvested from the patient's allogeneic HLA-matched sibling donors and placed over non-healing wounds (2-5). One case described global improvement in affected skin distant from the site of skin graft application, allowing for tapering of immunosuppressive medications. This suggests potential induction of tolerance by immune cells within the donated skin.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria - Patient (Recipient)

• Subjects will be eligible to participate in the study if all of the following conditions exist:
• Diagnosis of chronic, sclerotic, cutaneous graft versus host disease with one or more areas of cutaneous sclerosis and
• More than 1 year after HCT with stable hematopoietic engraftment and original transplant donor is available and agrees to be the epidermal donor for this study
• Stable (mixed or full) donor hematopoietic engraftment
• Original transplant donor is available and willing to be the epidermis donor
• Site for skin grafting free of cellulitis or other evidence of infection
• Insurance pre-authorization for procedure
• Voluntary written consent prior to any research related procedures or treatment.

Inclusion Criteria - Donor

• Age > 18 years (based on prior safety testing of the device)
• Healthy on physical examination in the opinion of the evaluating physician
• Known negativity for Hepatitis B and C, HIV, and HTLV1/2
• Voluntary written consent prior to any research related procedures

Exclusion Criteria

Subjects will be excluded from participation in the study if any of the following conditions exist:

• Patient with cutaneous infection
• Patient with recent change in medical management of chronic cutaneous GVHD (new medication or therapy, or change in dosing of existing medication) within one month of start date.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active treatment; This is an open label, single-institution pilot study to evaluate local response to split-thickness skin grafts from a matched bone marrow donor to chronic GVHD-affected skin in a hematopoietic stem cell transplant patient.	Device: CelluTome® Epidermal Harvesting System; split-thickness skin grafts from a matched bone marrow donor using the CelluTome® Epidermal Harvesting System; Other Names: split-thickness skin grafts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CGAA	Evaluation of clinical improvement in inflammation and sclerosis based on visual inspection and photodocumentation with outcome outcomes determined using the Chronic GVHD Activity Assessment (CGAA) to measure therapeutic response. The CGAA is an 8-item assessment measuring symptom severity of GVHD on a scale from 0 (not present) to 10 (as bad as you can imagine). Global score is calculated by summing items.	Change from baseline up to 12 months
Change in ELISA Markers of GVHD	Chronic GVHD lesions will be assessed following transplantation through serum ELISA assays of elafin and CXCL10 (validated biomarkers for assessment of GVHD disease activity)	Change from baseline up to 12 months

Collaborators and Investigators

• Sponsor: University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 15, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: DERM-2016-25255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No