Immunotherapy With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

Human Papillomavirus Clinical Trial

Official title: A Phase I Study of Immunotherapy With E6 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

Status Terminated

Clinical Trial Summary

Background:

Vulvar high-grade squamous intraepithelial lesion (HSIL) is caused by infection of the vulva with human papillomavirus (HPV). In a small percentage of cases, vulvar HSIL can turn into cancer. The risk of cancer can be reduced by treating HSIL. A personalized immune treatment might rid the body of HPV infection and thereby cure vulvar HSIL. The immune treatment in this study is called T cell therapy. The cells are E6 T Cell Receptor (TCR) T cells. Participants will also get aldesleukin (IL-2) to help the cells last longer.

Objective:

To find a safe dose of E6 TCR T cells combined with aldesleukin to use in people with vulvar HSIL.

Eligibility:

Design:

Participants will be screened with:

Physical exam

Medical history

Blood, lab, and pregnancy tests

Heart tests

Chest x-ray

Sample of tissue taken from the vulva (biopsy).

Participants will have leukapheresis. Blood will be removed by a needle in one arm. A machine removes white blood cells from the blood. The rest of the blood is returned by needle in the other arm. The white blood cells will be changed into E6 TCR T cells and grown in a lab. About 3 weeks later, participants will be admitted to the hospital for about 5 days. They will get the cells through a tube placed in a vein. They will get IL-2 the same way. Participants will recover 1-3 days in the hospital. They will be monitored closely. They will have blood and lab tests. Participants will have follow-up visits with lab tests and a physical exam every few months for 5 years. At some visits they will also have leukapheresis, blood tests, or vulvar biopsy.

Clinical Trial Description

Background:

• Vulvar high-grade squamous intraepithelial lesion (HSIL) is a premalignant epithelial lesion that is frequently multifocal and/or recurrent.

• The primary treatment is surgery, which may result in disfigurement and compromise of the urethra, anus, or clitoris. Recurrence after surgery is common and primarily treated with additional surgery.

• Vulvar HSIL is caused by chronic infection with the human papillomavirus (HPV) type 16 infection. In this clinical trial the HPV-16 infection is targeted with a single infusion of autologous T cells that have been genetically engineered to express an HPV-16 E6-specific

T cell receptor (E6 TCR T cells).

Objective:

-Determine the safety of E6 TCR T cells for the treatment of vulvar HSIL.

Eligibility:

• Histologically confirmed diagnosis of HPV-16+ vulvar HSIL.

• Expression of the human leukocyte antigen (HLA)-A2*02:01 allele.

• Measurable lesion(s) that are recurrent or cannot be resected with acceptable cosmetic or functional results.

• Age greater than or equal to 18 years old and less than or equal to 65 years old.

• Eastern Oncology Cooperative Group Performance Score of 0 or 1.

Design:

• This is a phase I clinical trial with a 3+3 dose escalation design.

• Subjects will receive E6 TCR T cells followed by up to two doses of aldesleukin 720,000 IU/kg intravenous (IV).

• No conditioning regimen will be given, aldesleukin will be capped at a maximum of two doses, and E6 TCR T cell dosing will begin at dose level -1 from the previously determined safe dose. ;

Related Conditions & MeSH terms

• High Grade Squamous Intraepithelial Lesion
• HPV-16
• Human Papillomavirus
• Squamous Intraepithelial Lesions of the Cervix

• NCT number: NCT03197025
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 1
• Start date: January 9, 2018
• Completion date: October 16, 2020