Clinical trial NCT04015947: Allogeneic Skin Grafting
Official title: Allogeneic Skin Grafting in the Treatment of Chronic Cutaneous Graft-versus-host Disease: a Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: GVHD
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2019-07-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in CGAA
timeFrame: Change from baseline up to 12 months
measure: Change in ELISA Markers of GVHD
timeFrame: Change from baseline up to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
References: