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

NCT05515692 | Withdrawn Early Phase 1 DMC FDA Drug

• 3 other identifiers: 21382NCI-2022-05914P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Incidence of disease specific response

  Up to day 168

• Incidence of disease specific response

  Up to day 168

Study Arms (1)

Treatment (electron beam radiotherapy)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Combination Product: Electron Beam Therapy; Procedure: High Frequency Ultrasound Imaging; Other: Questionnaire Administration; Radiation: Radiation Therapy Treatment Planning and Simulation; Procedure: Skin Biopsy

Interventions

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (electron beam radiotherapy)

Computed Tomography PROCEDURE

Undergo radiotherapy simulation using CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (electron beam radiotherapy)

Electron Beam Therapy COMBINATION_PRODUCT

Undergo electron beam radiotherapy

Treatment (electron beam radiotherapy)

High Frequency Ultrasound Imaging PROCEDURE

Undergo HFUS

Also known as: HFUS

Treatment (electron beam radiotherapy)

Questionnaire Administration OTHER

Ancillary studies

Treatment (electron beam radiotherapy)

Radiation Therapy Treatment Planning and Simulation RADIATION

Undergo radiotherapy simulation using clinical setup

Also known as: Radiation Therapy Treatment Planning/Simulation

Treatment (electron beam radiotherapy)

Skin Biopsy PROCEDURE

Undergo biopsy

Also known as: Biopsy of Skin

Treatment (electron beam radiotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Interventions

Specimen Handling

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Karamjeet S Sandhu

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 25, 2022
• Study Start: June 30, 2024
• Primary Completion: September 18, 2024
• Study Completion: September 18, 2024
• Last Updated: July 23, 2024

Record last verified: 2024-07