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

NCT ID: NCT05515692

Last Updated: 2024-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

EARLY_PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-30

Study Completion Date

2024-09-18

Brief Summary

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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

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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

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (electron beam radiotherapy)

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Correlative studies

Computed Tomography

Intervention Type PROCEDURE

Undergo radiotherapy simulation using CT

Electron Beam Therapy

Intervention Type COMBINATION_PRODUCT

Undergo electron beam radiotherapy

High Frequency Ultrasound Imaging

Intervention Type PROCEDURE

Undergo HFUS

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Radiation Therapy Treatment Planning and Simulation

Intervention Type RADIATION

Undergo radiotherapy simulation using clinical setup

Skin Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Interventions

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Biospecimen Collection

Correlative studies

Intervention Type PROCEDURE

Computed Tomography

Undergo radiotherapy simulation using CT

Intervention Type PROCEDURE

Electron Beam Therapy

Undergo electron beam radiotherapy

Intervention Type COMBINATION_PRODUCT

High Frequency Ultrasound Imaging

Undergo HFUS

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Radiation Therapy Treatment Planning and Simulation

Undergo radiotherapy simulation using clinical setup

Intervention Type RADIATION

Skin Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography HFUS Radiation Therapy Treatment Planning/Simulation Biopsy of Skin

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karamjeet S Sandhu

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Other Identifiers

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NCI-2022-05914

Identifier Type: REGISTRY

Identifier Source: secondary_id

21382

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21382

Identifier Type: -

Identifier Source: org_study_id

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