Squamous Lntraepithelial Lesions of VulvaPhase 2NCT03937791
Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions
A Phase 2 study testing E7 T Cell Receptor (TCR) in people with Squamous Lntraepithelial Lesions of Vulva and Neoplasms, Squamous Cell, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Lntraepithelial Lesions of Vulva, Neoplasms, Squamous Cell, Vulvar HSIL
- What is being tested?
- E7 T Cell Receptor (TCR)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Oct 2019to 22 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 25Show fewer
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Study of Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions
Background:
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.
Read more
Objective:
To test if a personalized immune treatment can cure vulvar HSIL.
Eligibility:
People ages 18 and older with vulvar HSIL that cannot be removed with surgery, or for which surgery has failed
Design:
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....
Read the detailed 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 a HPV-16 E7-specific T cell receptor (E7 TCR T cells).
Objective:
-Determine the complete response rate for E7 TCR T cells in 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.
- Eastern Oncology Cooperative Group Performance Score of 0 or 1.
Design:
- 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.
- Being tested
- E7 T Cell Receptor (TCR)
- Keywords
- Human Papilloma Virus (HPV) Type 16, Retroviral Vector Supernatant, Leukapheresis, T Cell Receptor, Premalignant Epithelial Lesion
- Medical subject headings
- Neoplasms, Squamous Cell, Papillomavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E7 T Cell Receptor (TCR)Biological
One dose of E7 TCR T cells (1x10^11 cells) will be administered intravenously over 20 to 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1/1x10^11 E7 T Cell Receptor (TCR) T cells | Experimental | 1x10^11 E7 TCR T cells will be administered intravenously over 20 to 30 minutes on day 0. Receives: Biological: E7 T Cell Receptor (TCR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
The fraction of patients who experience a complete response. Complete Response is disappearance of all target lesions. No appearance of new lesions.
Measured: 3 months
Secondary outcomes (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
Grade 2 adverse event is moderate.
Measured: 30 days following the last dose of study therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start9 Oct 2019
- Primary completion22 Jun 2020
- Study completion22 Jun 2020
Why it stopped: 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Lntraepithelial Lesions of VulvaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Scott Norberg, D.O., National Cancer Institute (NCI)
- Investigators
- Scott Norberg, D.O., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937791
- Sponsor's protocol ID
- 190091
- Other IDs
- 19-C-0091
- Status last verified
- Mar 2021
- First submitted
- 3 May 2019
- Last updated
- 13 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions
- ClinicalTrials.gov ID
- NCT03937791
- Acronym / sponsor ID
- 190091
- Keywords
- Human Papilloma Virus (HPV) Type 16, Retroviral Vector Supernatant, Leukapheresis, T Cell Receptor, Premalignant Epithelial Lesion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 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
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 9 Oct 2019 (actual)
- Primary completion
- 22 Jun 2020 (actual)
- Study completion
- 22 Jun 2020 (actual)
- First posted
- 6 May 2019 (actual)
- Results
- Posted 18 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
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.
Objective:
To test if a personalized immune treatment can cure vulvar HSIL.
Eligibility:
People ages 18 and older with vulvar HSIL that cannot be removed with surgery, or for which surgery has failed
Design:
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....
Detailed 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 a HPV-16 E7-specific T cell receptor (E7 TCR T cells).
Objective:
-Determine the complete response rate for E7 TCR T cells in 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.
- Eastern Oncology Cooperative Group Performance Score of 0 or 1.
Design:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1/1x10^11 E7 T Cell Receptor (TCR) T cells | Experimental | Biological: E7 T Cell Receptor (TCR)1x10^11 E7 TCR T cells will be administered intravenously over 20 to 30 minutes on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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:
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E7 T Cell Receptor (TCR)One dose of E7 TCR T cells (1x10^11 cells) will be administered intravenously over 20 to 30 minutes. | Biological | Arm 1/1x10^11 E7 T Cell Receptor (TCR) T cells |
Primary outcome
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.
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Norberg, D.O. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing E7 T Cell Receptor (TCR) in people with Squamous Lntraepithelial Lesions of Vulva and Neoplasms, Squamous Cell, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2021.