Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions
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|ClinicalTrials.gov 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
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:
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|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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.
- 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.
- 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.
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT03937791
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Scott Norberg, D.O.||National Cancer Institute (NCI)|