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

Malignant Solid Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05515692
• Other study ID #: 21382
• Secondary ID: NCI-2022-0591421
• Status: Suspended
• Phase: Early Phase 1
• Start date: June 30, 2024
• Est. completion date: September 18, 2024

Study information

• Verified date: January 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 14
• Est. completion date: September 18, 2024
• Est. primary completion date: September 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Graft vs Host Disease
• Hematopoietic and Lymphoid System Neoplasm
• Malignant Solid Neoplasm
• Neoplasms

Intervention

Procedure:
• Biospecimen Collection
Correlative studies
• 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

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of toxicity	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.	From study initiation of study treatment to day 28
Secondary	Incidence of disease specific response	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.	Up to day 168
Secondary	Incidence of disease specific response	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.	Up to day 168