| Eligibility |
- INCLUSION CRITERIA:
- Patients must have vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) as
confirmed by pathology report from a Clinical Laboratory Improvement Amendments
(CLIA)-certified laboratory.
- Vulvar HSIL must be human papillomavirus (HPV)-16+ by a polymerase chain reaction
(PCR), Ribonucleic acid (RNA), or in situ hybridization test from a CLIA certified
laboratory.
- Patients must have measurable lesion(s) as defined in one or more of the following
criteria:
- Failure of surgery to control disease (i.e. positive margins after surgery or
recurrence of HSIL after surgery).
- Multifocal or extensive disease for which surgery would result in disfigurement
that is not be acceptable to the patient.
- Disease for which surgery would have a risk of functional impairment that is not
be acceptable to the patient (i.e. involve partial or complete excision of the
clitoris, anus, vagina, or urethra).
- Patients may have received any previous therapy, including surgical excision. Patients
with recurrent disease must have histologically documented recurrence on new biopsy
and a measurable lesion that meets the above criteria.
- Patients must have the human leukocyte antigen (HLA)-A*02:01 allele
- Age greater than or equal to18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Able to understand and sign the Informed Consent Document.
- Women of child-bearing potential must have a negative pregnancy test. Women of
child-bearing potential are defined as all women who are not post-menopausal or who
have not had a hysterectomy. Postmenopausal will be defined as women over the age of
55 who have not had a menstrual period in at least 1 year.
- The effects of E7 T-Cell Receptor (TCR) T Cells on the developing human fetus are
unknown. For this reason, women of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while she is participating in this study, she should inform
her treating physician immediately.
- Seronegative for human immunodeficiency virus (HIV) antibody. The experimental
treatment being evaluated in this protocol depends on an intact immune system.
Patients who are HIV seropositive can have decreased immune-competence and thus be
less responsive to the experimental treatment.
- Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody
test is positive, then the patient must be tested for the presence of antigen by
reverse transcription (RT)-PCR and be hepatitis C virus (HCV) RNA negative.
- Must be willing to participate in Gene Therapy Long Term Followup Protocol
(20-C-0051), which will follow patients for up to 15 years per Food and Drug
Administration (FDA) requirements.
- Patients must have normal organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,000/mcL
- platelets greater than or equal to 100,000/mcL
- hemoglobin greater than or equal to 9.0 g/dL
- total bilirubin within 1.5X normal institutional limits except in patients with
Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL
- Aspartate Aminotransferase (AST)/Serum glutamic-oxaloacetic
transaminase(SGOT)/Alanine Aminotransferase (ALT)/Serum glutamic pyruvic
transaminase,(SGPT) Serum ALT/AST < 3X upper limit of normal (ULN)
- creatinine < 1.5X baseline, < 1.5X ULN OR
- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients
with creatinine levels above institutional normal (by the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation)
EXCLUSION CRITERIA:
- Patients who are receiving any other investigational agents
- Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with E7 TCR, breastfeeding should be discontinued
if the mother is treated with E7 TCR. These potential risks may also apply to other
agents used in this study.
- Uncontrolled intercurrent illness including, but not limited to, any ongoing or active
infection (e.g. requiring anti-infective therapy), coagulation disorders,
cardiovascular disorders, respiratory disorders, cancer, or psychiatric illness/social
situations (within the last six months) that would limit compliance with study
requirements.
- Any form of systemic immunodeficiency, including acquired deficiency such as HIV or
primary immunodeficiency such as Severe Combined Immunodeficiency Disease. The
experimental treatment being evaluated in this protocol depends on an intact immune
system. Patients who have decreased immune competence maybe less responsive to the
treatment.
- Concurrent systemic steroid therapy if greater than the equivalent of 5 mg prednisone
by mouth (PO) daily. Patients previously on steroids must be off steroids for four
weeks prior to treatment.
- Cardiac stress test and pulmonary function tests maybe required for patients with a
clinical history of significat cardiopulmonary disease. Patients with active cardiac
ischemia or severe chronic obstructive pulmonary disease are not eligible.
- Patients with any active invasive cancer are not eligible.
- Patients with vulvar HSIL that is not HPV-16+ or is associated with multiple types of
high-risk HPV at the time of eligibility assessment are not eligible.
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