Subjects With Severe, Refractory Sclerotic Skin Changes
Conditions
Brief summary
Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplant.Chronic GVHD is characterized by skin thickening and tightening. Advanced sclerosis can lead to reduced range of motion and incapacitating joint contractures. Once present, there are few therapeutic options. We will treat sclerosis and limb contractures with an ablative fractional laser, a device FDA-approved for scar treatment. This approach has successfully treated contracturesdue to burn scars.
Interventions
DEVICECO2 Laser
Perform ablative fractional resurfacing using a 10,600nm carbon dioxide (CO2) laser targeted to thickened, sclerotic plaques causing range of motion limitation and contracture across joints.
RADIATIONUltrasound
Patients will undergo ultrasound of the planned treatment site to measure skin thickness and blood flow via Doppler ultrasound.
DIAGNOSTIC_TESTSkin Biopsy
standard 4mm punch biopsy of the skin at the planned treatment site for histologic assessment of skin thickness and sclerosis.
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be able to give informed consent * All adult patients (18 years of age or older) Severe sclerotic skin changes of chronic graft versus host disease meeting a score of 3 on the NIH consensus criteria for organ scoring of chronic GVHD, * a score defined by deep sclerotic features with hidebound skin which cannot be pinched together, resulting in impaired motion. * According to the NIH criteria, the patient need not have widespread cutaneous GVHD; hidebound skin OR impaired mobility receive a score of 3 (highest score). * Demonstrable range of motion limitations and joint contractures due to sclerotic GVHD across a specific joint / limb amenable to laser therapy must be present. - - Patients must note an inability to bend the joint (e.g. foot, wrist, elbow) freely which compromises the ability to perform specific tasks (e.g. walking up or down stairs, grabbing / making a fist, lifting or raising thearms over the head). As these functional limitations are by their nature subjective (and NIH scoring criteria are themselves subjective) determination of eligibility will be made by the investigator. * ECOG Performance Status shall be 0-3
Exclusion criteria
* Persons unable to provide informed consent Pregnant or nursing women, or children under age 18 * Active infections such as herpes simplex virus (HSV) Acute, untreated medical problems such as poorly-controlled diabetes, decompensated heart failure, etc. * There are no specific contraindications to use of the laser based on skin pigmentation, sun sensitivity, history of keloids, use of specific medications, etc. * Appropriateness for trial entry will be determined on an individual basis by the study investigators. * Patients with ECOG Performance Status 3 will be excluded. * Patients with ANC 1500,PLT 50, or Hgb 8.0 will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Show Improvement in Range of Motion, Flexion, and Extension | 5 months from time point zero / baseline | Range of motion (flexion, extension, supination, pronation) of the target joint (measured in degrees, using a goniometer). |
| Number of Subjects With Evidence of Collagen Remodeling (Increased Dermal Echogenicity) Compared to Baseline | 3 months after final laser session (5 months after time zero / baseline) | Measurement of skin echogencity (brightness) in comparison with pre-therapy images of the same areas using high-resolution ultrasound. |
| Number of Subjects Who Show Decrease in Skin Thickness and Sclerosis With Collagen Remodeling as Measured by Before and After Skin Biopsies Biopsy | baseline and 3 months after final laser session | Trichcrome stain, collagen fiber number and thickness, Herovici stain, elastic fiber length, and dermal thickness. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rAblative Fractional Laser for Sclerotic GVHD-Associated Joint Range of motion limitations and joint contractures due to sclerotic GVHD across a specific joint / limb
CO2 Laser: Perform ablative fractional resurfacing using a 10,600nm carbon dioxide (CO2) laser targeted to thickened, sclerotic plaques causing range of motion limitation and contracture across joints.
Ultrasound: Patients will undergo ultrasound of the planned treatment site to measure skin thickness and blood flow via Doppler ultrasound.
Skin Biopsy: standard 4mm punch biopsy of the skin at the planned treatment site for histologic assessment of skin thickness and sclerosis.
Photography: Photography of the affected area / intended treatment area. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | rAblative Fractional Laser for Sclerotic GVHD-Associated Joint |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Number of Subjects Who Show Decrease in Skin Thickness and Sclerosis With Collagen Remodeling as Measured by Before and After Skin Biopsies Biopsy
Trichcrome stain, collagen fiber number and thickness, Herovici stain, elastic fiber length, and dermal thickness.
Time frame: baseline and 3 months after final laser session
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAblative Fractional Laser for Sclerotic GVHD-Associated Joint | Number of Subjects Who Show Decrease in Skin Thickness and Sclerosis With Collagen Remodeling as Measured by Before and After Skin Biopsies Biopsy | 6 Participants |
Primary
Number of Subjects Who Show Improvement in Range of Motion, Flexion, and Extension
Range of motion (flexion, extension, supination, pronation) of the target joint (measured in degrees, using a goniometer).
Time frame: 5 months from time point zero / baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAblative Fractional Laser for Sclerotic GVHD-Associated Joint | Number of Subjects Who Show Improvement in Range of Motion, Flexion, and Extension | 6 Participants |
Primary
Number of Subjects With Evidence of Collagen Remodeling (Increased Dermal Echogenicity) Compared to Baseline
Measurement of skin echogencity (brightness) in comparison with pre-therapy images of the same areas using high-resolution ultrasound.
Time frame: 3 months after final laser session (5 months after time zero / baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAblative Fractional Laser for Sclerotic GVHD-Associated Joint | Number of Subjects With Evidence of Collagen Remodeling (Increased Dermal Echogenicity) Compared to Baseline | 6 Participants |