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

Primary Purpose

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

Status

Not yet recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Biospecimen Collection

Computed Tomography

Electron Beam Therapy

High Frequency Ultrasound Imaging

Questionnaire Administration

Radiation Therapy Treatment Planning and Simulation

Skin Biopsy

About this trial

This is an interventional treatment trial for Hematopoietic and Lymphoid System Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (electron beam radiotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT05515692

First Posted

August 17, 2022

Last Updated

July 24, 2023

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT05515692

Brief Title

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

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 30, 2023 (Anticipated)

Primary Completion Date

September 18, 2024 (Anticipated)

Study Completion Date

September 18, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (electron beam radiotherapy)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Biospecimen Collection

Other Intervention Name(s)

Biological Sample Collection, Biospecimen Collected, Specimen Collection

Intervention Description

Correlative studies

Intervention Type

Procedure

Intervention Name(s)

Computed Tomography

Other Intervention Name(s)

CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Intervention Description

Undergo radiotherapy simulation using CT

Intervention Type

Combination Product

Intervention Name(s)

Electron Beam Therapy

Intervention Description

Undergo electron beam radiotherapy

Intervention Type

Procedure

Intervention Name(s)

High Frequency Ultrasound Imaging

Other Intervention Name(s)

HFUS

Intervention Description

Undergo HFUS

Intervention Type

Other

Intervention Name(s)

Questionnaire Administration

Intervention Description

Ancillary studies

Intervention Type

Radiation

Intervention Name(s)

Radiation Therapy Treatment Planning and Simulation

Other Intervention Name(s)

Radiation Therapy Treatment Planning/Simulation

Intervention Description

Undergo radiotherapy simulation using clinical setup

Intervention Type

Procedure

Intervention Name(s)

Skin Biopsy

Other Intervention Name(s)

Biopsy of Skin

Intervention Description

Undergo biopsy

Primary Outcome Measure Information:

Title

Incidence of toxicity

Description

Time Frame

From study initiation of study treatment to day 28

Secondary Outcome Measure Information:

Title

Incidence of disease specific response

Description

Time Frame

Up to day 168

Title

Incidence of disease specific response

Description

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.

Time Frame

Up to day 168

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Karamjeet S Sandhu

Organizational Affiliation

City of Hope Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

City of Hope Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Karamjeet S. Sandhu

Phone

626-218-2405

ksandhu@coh.org

First Name & Middle Initial & Last Name & Degree

Karamjeet S. Sandhu

12. IPD Sharing Statement

Learn more about this trial

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

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