NCT05515692

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

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Hematopoietic and Lymphoid System Neoplasm
• Malignant Solid Neoplasm
• Refractory Sclerodermatous Graft Versus Host Disease

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Correlative studies
PROCEDURE	Computed Tomography	Undergo radiotherapy simulation using CT
COMBINATION_PRODUCT	Electron Beam Therapy	Undergo electron beam radiotherapy
PROCEDURE	High Frequency Ultrasound Imaging	Undergo HFUS
OTHER	Questionnaire Administration	Ancillary studies
RADIATION	Radiation Therapy Treatment Planning and Simulation	Undergo radiotherapy simulation using clinical setup
PROCEDURE	Skin Biopsy	Undergo biopsy

Timeline

• Start date: 2024-06-30
• Primary completion: 2024-09-18
• Completion: 2024-09-18
• First posted: 2022-08-25
• Last updated: 2024-07-23

Regulatory

• FDA-regulated drug study