Clinical trial NCT05515692: Electron Beam Radiotherapy for the Treatment of Refractory Sclerodermatous Chronic Graft Versus Host Disease
Official title: Pilot Study of Safety and Feasibility of Electron Beam Radiotherapy to Treat Refractory Sclerodermatous Chronic Graft-versus-Host Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Hematopoietic and Lymphoid System Neoplasm
Malignant Solid Neoplasm
Refractory Sclerodermatous Graft Versus Host Disease
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-08-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Documented informed consent of the participant and/or legally authorized representative
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  * If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Permitting to perform clinical photography
* Age: \>= 18 years
* Histologically confirmed sclerodermatous GHVD
* Relapsed/refractory sclerodermatous cGVHD
* Measurable disease of at least 2.0 cm
* Failed at least \>= 2 prior frontline therapies for sclerodermatous chronic GvHD
* Fully recovered from the acute toxic effects (except alopecia) to =\< Grade 1 to prior therapy
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

  * To be performed within 7 days prior to Day 1 of protocol therapy unless otherwise stated
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 month after the last dose of protocol therapy

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to Day 1 of protocol therapy
* Herbal medications
* Females only: Pregnant or breastfeeding
* Inability to comprehend and sign inform consent
* Individuals known to carry germline gene mutations in TP53, NBS and ATM.
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Primary outcomes:
measure: Incidence of toxicity
timeFrame: From study initiation of study treatment to day 28
Secondary outcomes:
measure: Incidence of disease specific response
timeFrame: Up to day 168
measure: Incidence of disease specific response
timeFrame: Up to day 168
Other outcomes:
Locations:
Study officials:
affiliation: City of Hope Medical Center
name: Karamjeet S Sandhu
role: PRINCIPAL_INVESTIGATOR
References: