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E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia

Phase 1
Withdrawn
Conditions
Cervical Intraepithelial Neoplasia
Interventions
Biological: E7 TCR
Registration Number
NCT04411134
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

Background:

Human papillomavirus (HPV) can lead to High-Grade Cervical Intraepithelial Neoplasia (CIN 2,3). This type of lesion has a high risk of becoming cancer. T cells are part of the immune system. A new type of treatment involves modifying these cells and injecting them into the lesions to shrink them.

Objective:

To test if injecting a type of treatment directly into cervical lesions can be safely given as therapy for high-grade CIN.

Eligibility:

People ages 21 and older with CIN 2,3 caused by HPV-16

Design:

Participants will be screened over at least 2 visits with:

Tumor sample

Blood and urine tests

Medical and medication history

Physical exam

Pelvic exam and colposcopy to look at the cervix

Participants will have a baseline visit. They may be admitted to the hospital. They may receive a large catheter inserted into a vein. They will have a vein assessment.

Before they receive treatment, participants will have a biopsy of the cervix. They will have leukapheresis. Blood will be removed through a needle in the arm, circulated through a machine that takes out the while blood cells, then returned through a needle in the other arm. A central catheter may also be used.

Participants will have the modified cells injected directly into their cervical lesions. They will recover in the hospital for 1-2 days.

Participants will have follow-up visits 2 weeks, 31 days, 6 weeks, and 12 weeks after treatment. They may receive a second injection at the 31-day visit.

Participants will be contacted once a year for 5 years after treatment. They will be followed for up to 15 years.

Detailed Description

Background:

* Cervical Intraepithelial Neoplasia (CIN) is caused by persistent infection with the Human Papillomavirus (HPV).

* High-grade lesions are common, affecting 5% of the female population in the United States, and are more likely to progress to cervical cancer.

* Surgical and ablative therapies are effective but can lead to long-term morbidity. New treatment modalities are needed.

* E7 TCR T cells have demonstrated safety and clinical activity in treatment-refractory metastatic HPV+ cancers.

Objectives:

- To determine the safety of intralesional injection of E7 TCR T cells as therapy for high- grade CIN.

Eligibility:

- Patients greater than or equal to 21 years of age with HPV16-associated, high-grade CIN.

Design:

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

* Patients will receive intralesional injections of E7 TCR T cells.

* Patients will not receive a conditioning chemotherapy regimen or systemic aldesleukin.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
Female
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Arm 1E7 TCRApproximately 3x10\^8 or 1.5x10\^9 E7 TCR T cells will be injected on day 0 and 1.5x10\^9 E7 TCR T cells on day 31 (2 escalating dose levels)
Arm 2E7 TCRThe MTD from among dose level 1 and dose level 2
Primary Outcome Measures
NameTimeMethod
To determine the safety of intralesional injection of E7 TCR T cell therapy for highgrade CIN3 months

The fraction who experience a DLT based on the dose level and cell administration within the dose level will be determined and reported.The analysis will be entirely descriptive.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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