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Bronchiolitis Obliterans

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Organizing Pneumonia

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Lung Diseases, Obstructive

Chronic Graft Versus Host Disease

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Bronchiolitis Obliterans Organizing Pneumonia

Patients undergo radiotherapy simulation on day -14 using either a clinical setup or CT simulation at the discretion of the treating radiation oncologist. Patients then undergo electron beam radiotherapy on day 0. Patients also undergo skin biopsies at baseline, day 28, and day 168 after radiotherapy, and high frequency ultrasound (HFUS) scans on days 28, 56, 84, 112, 140, and 168 after radiotherapy.

Biospecimen Collection

Computed Tomography

Electron Beam Therapy

High Frequency Ultrasound Imaging

Questionnaire Administration

Undergo radiotherapy simulation using clinical setup

Radiation Therapy Treatment Planning and Simulation

Skin Biopsy

Karamjeet S Sandhu

This clinical trial tests the safety and side effects of a single small dose (fraction) of electron beam radiotherapy (e-BRT) at 10 Gy dose in treating patients with refractory (did not respond to other treatments) sclerodermatous chronic graft versus host disease (GVHD). GVHD is the most common complication after bone marrow transplant from a donor and happens as a result of donor immune cells attacking patients cells. Fibroblasts are skin cells that produce collagen and fibers and are the cells mainly involved in development of skin GVHD. Previous research has shown that fibroblasts can become fibrocytes (inactive fibroblast) at the fastest rate after receiving 8 Gy or more radiation. Moreover, regulatory T cells (Tregs) are cells from the immune system that can control GVHD and previous research has shown that radiation can increase the number of Tregs. Therefore, e-BRT at 10 Gy has the potential to improve GVHD by increasing the fibroblast to fibrocyte speed and the number of Tregs.

PRIMARY OBJECTIVE:

I. To establish safety of 10 Gy of 6 MeV electron beam radiotherapy (e-BRT) administration in subjects with refractory sclerodermatous chronic graft-versus-host disease (cGVHD).

SECONDARY OBJECTIVE:

I. To provide preliminary efficacy data on the anti-fibrotic effects of e-BRT treatment at 4 and 24 weeks.

EXPLORATORY OBJECTIVES:

I. To evaluate the skin microenvironment 21 days before (baseline) and 28, and 168 days after e-BRT administration by assessing the presence and percentage of immune cell subsets (including but not limited to Th17 and Treg cells), presence of fibroblast and fibrocytes, and changes in the vasculature as measured by microvessel density (MVD) by CD31 and VEGF staining in tissue microarrays (TMA).

II. To assess changes in the presence and levels of GVHD inflammatory biomarkers and cytokines (including but not limited to IL-17A, IL-21, and IL-2) in patients' plasma after treatment with e-BRT.

OUTLINE:

Patients undergo radiotherapy simulation on day -14 using either a clinical setup or computed tomography (CT) simulation at the discretion of the treating radiation oncologist. Patients then undergo electron beam radiotherapy on day 0. Patients also undergo skin biopsies at baseline, day 28, and day 168 after radiotherapy, and high frequency ultrasound (HFUS) scans on days 28, 56, 84, 112, 140, and 168 after radiotherapy.

After completion of the study, patients are followed up yearly.

Electron Beam Radiotherapy for the Treatment of Refractory Sclerodermatous Chronic Graft Versus Host Disease

Pilot Study of Safety and Feasibility of Electron Beam Radiotherapy to Treat Refractory Sclerodermatous Chronic Graft-versus-Host Disease

Will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Unacceptable toxicity (UT) is defined as any local toxicity at the level of the treatment portal that is greater or equal to Grade 3 per National Cancer Institute (NCI) CTCAE version 5.0. The observation window of UT is from receiving study treatment until day 28 or observation of UT, whichever comes first. Patients who receive study treatment and complete UT evaluation will be evaluable for UT. Patients who are inevaluable for UT will be replaced. Toxicity information recorded in each patient will include the type, severity, and the probable association with electron beam radiotherapy (eBRT). Tables will be constructed to summarize the observed incidence by severity and type of toxicity, and dose levels. All patients who receive eBRT will be included as part of an 'as treated' analysis, in toxicities/complications.

Disease-specific response criteria including, but not limited to: complete response (CR) and partial response (PR) according to the core clinician-assessed and patient-reported chronic graft versus host disease (GVHD)-specific measures recommended by National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: IV. The 2014 Response Criteria Working Group Report and modified Rodnan skin score, and 20 MHz ultrasound (US). The cumulative incidence of relapse/progression will be calculated as competing risks.

Disease-specific response criteria including, but not limited to: complete response (CR) and partial response (PR) according to the core clinician-assessed and patient-reported chronic graft versus host disease (GVHD)-specific measures recommended by National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: IV. The 2014 Response Criteria Working Group Report and modified Rodnan skin score, and 20 MHz ultrasound (US). The cumulative incidence of non-relapse mortality will be calculated as competing risks.

National Cancer Institute (NCI)

City of Hope Medical Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Electron Beam Radiotherapy for the Treatment of Refractory Sclerodermatous Chronic Graft Versus Host Disease	NCT05515692	Hematopoietic a... Malignant Solid... Refractory Scle...	Biospecimen Col... Computed Tomogr... Electron Beam T... High Frequency ... Questionnaire A... Radiation Thera... Skin Biopsy	18 Years -	City of Hope Medical Center
Electron Beam Radiotherapy for the Treatment of Refractory Sclerodermatous Chronic Graft Versus Host Disease	NCT05515692	Hematopoietic a... Malignant Solid... Refractory Scle...	Biospecimen Col... Computed Tomogr... Electron Beam T... High Frequency ... Questionnaire A... Radiation Thera... Skin Biopsy	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for refractory sclerodermatous graft versus host disease