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Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03937791
Recruitment Status : Terminated (All analysis with identifiable specimens/data is complete or site has no identifiers linked to the specimens/data. The one enrolled pt has been taken off study)
First Posted : May 6, 2019
Results First Posted : March 18, 2021
Last Update Posted : April 13, 2021
Information provided by (Responsible Party):
Scott Norberg, D.O., National Cancer Institute (NCI)

Brief Summary:


Human papillomavirus (HPV) can cause vulvar high-grade squamous intraepithelial lesions (HSIL). Sometimes, this can become cancer. Researchers want to see if T cell therapy can treat vulvar HSIL. In this therapy, a person s immune cells are genetically modified so they can attack the HPV.


To test if a personalized immune treatment can cure vulvar HSIL.


People ages 18 and older with vulvar HSIL that cannot be removed with surgery, or for which surgery has failed


Participants will be screened with:

Medical history

Physical exam

HPV testing

Venous assessment

Chest x-ray

Heart and pulmonary tests

Participants will have a baseline visit. They may have a vulvar biopsy. Photographs will be taken of their lesions.

Participants will have leukapheresis: Blood is removed from a needle in the arm and circulated through a machine that takes out the white blood cells. The other blood cells are returned through a needle in the other arm. The white blood cells will be used to grow treatment cells.

Participants will receive the treatment through a tube inserted into an arm, neck, or chest vein. They will recover in the hospital for 1 to 2 days. They will have blood tests and take supportive medications.

Participants may have one more treatment.

Participants will have 5 follow-up visits in the first 3 months after treatment. They may have more visits if their disease is growing. Visits will include blood tests. They may include vulvar biopsies or leukapheresis.

Participants will have an annual physical exam for 5 years after treatment that can be done at home or at the National Institutes of Health (NIH). Then they will have an annual phone or email questionnaire for another 10 years....

Condition or disease Intervention/treatment Phase
Squamous Lntraepithelial Lesions of Vulva Neoplasms, Squamous Cell Vulvar HSIL Biological: E7 T Cell Receptor (TCR) Phase 2

Detailed Description:


  • 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 a HPV-16 E7-specific T cell receptor (E7 TCR T cells).


-Determine the complete response rate for E7 TCR T cells in the treatment of vulvar HSIL.


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


  • This is a phase II clinical trial
  • Simon minimax two-stage design with initial enrollment of 12 patients and expansion to 16 patients if one or more complete response(s) is/are observed in the initial patients.
  • Subjects will receive 1x10^11 E7 TCR T cells
  • No conditioning regimen or aldesleukin will be given
  • Re-enrollment will be allowed for a small number of subjects.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions
Actual Study Start Date : October 9, 2019
Actual Primary Completion Date : June 22, 2020
Actual Study Completion Date : June 22, 2020

Arm Intervention/treatment
Experimental: Arm 1/1x10^11 E7 T Cell Receptor (TCR) T cells
1x10^11 E7 TCR T cells will be administered intravenously over 20 to 30 minutes on day 0.
Biological: E7 T Cell Receptor (TCR)
One dose of E7 TCR T cells (1x10^11 cells) will be administered intravenously over 20 to 30 minutes.

Primary Outcome Measures :
  1. Fraction of Participants With Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Who Experience a Complete Response for E7 T-Cell Receptor (TCR) T Cells Treatment [ Time Frame: 3 months ]
    The fraction of patients who experience a complete response. Complete Response is disappearance of all target lesions. No appearance of new lesions.

Secondary Outcome Measures :
  1. Number of Grade 2 Adverse Events Unlikely Related to Drug in Participants Who Received E7 T-Cell Receptor (TCR) T Cells Administered in a Low Intensity Setting Without Conditioning or Systemic Aldesleukin [ Time Frame: 30 days following the last dose of study therapy ]
    Grade 2 adverse event is moderate.

Other Outcome Measures:
  1. Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [ Time Frame: Date treatment consent signed to date off study, approximately 8 months and 6 days. ]
    Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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)


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03937791

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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Scott Norberg, D.O. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Scott Norberg, D.O., National Cancer Institute (NCI):
Additional Information:
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Responsible Party: Scott Norberg, D.O., Principal Investigator, National Cancer Institute (NCI) Identifier: NCT03937791    
Other Study ID Numbers: 190091
First Posted: May 6, 2019    Key Record Dates
Results First Posted: March 18, 2021
Last Update Posted: April 13, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Scott Norberg, D.O., National Cancer Institute (NCI):
Human Papilloma Virus (HPV) Type 16
Retroviral Vector Supernatant
T Cell Receptor
Premalignant Epithelial Lesion
Additional relevant MeSH terms:
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Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type