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出境医 / 临床实验 / Allogeneic Skin Grafting

Allogeneic Skin Grafting

Study Description
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.

Condition or disease Intervention/treatment Phase
GVHD Device: CelluTome® Epidermal Harvesting System Not Applicable

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Device Feasibility
Official Title: Allogeneic Skin Grafting in the Treatment of Chronic Cutaneous Graft-versus-host Disease: a Pilot Study
Actual Study Start Date : August 1, 2019
Actual Primary Completion Date : April 1, 2021
Actual Study Completion Date : April 1, 2021
Arms and Interventions
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 Name: split-thickness skin grafts

Outcome Measures
Primary Outcome Measures :
  1. Change in CGAA [ Time Frame: Change from baseline up to 12 months ]
    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.

  2. Change in ELISA Markers of GVHD [ Time Frame: Change from baseline up to 12 months ]
    Chronic GVHD lesions will be assessed following transplantation through serum ELISA assays of elafin and CXCL10 (validated biomarkers for assessment of GVHD disease activity)


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations

Locations
Layout table for location information
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55414
Sponsors and Collaborators
University of Minnesota
Tracking Information
First Submitted Date  ICMJE August 7, 2018
First Posted Date  ICMJE July 11, 2019
Last Update Posted Date April 20, 2021
Actual Study Start Date  ICMJE August 1, 2019
Actual Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Change in CGAA [ Time Frame: Change from baseline up to 12 months ]
    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 in ELISA Markers of GVHD [ Time Frame: Change from baseline up to 12 months ]
    Chronic GVHD lesions will be assessed following transplantation through serum ELISA assays of elafin and CXCL10 (validated biomarkers for assessment of GVHD disease activity)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Skin Grafting
Official Title  ICMJE Allogeneic Skin Grafting in the Treatment of Chronic Cutaneous Graft-versus-host Disease: a Pilot Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Device Feasibility
Condition  ICMJE GVHD
Intervention  ICMJE Device: CelluTome® Epidermal Harvesting System
split-thickness skin grafts from a matched bone marrow donor using the CelluTome® Epidermal Harvesting System
Other Name: split-thickness skin grafts
Study Arms  ICMJE 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.
Intervention: Device: CelluTome® Epidermal Harvesting System
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 15, 2021)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2019)
5
Actual Study Completion Date  ICMJE April 1, 2021
Actual Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04015947
Other Study ID Numbers  ICMJE DERM-2016-25255
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Minnesota
Study Sponsor  ICMJE University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Minnesota
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP