Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Infections

Skin and Connective Tissue Diseases

Uterine Cervical Neoplasms

Condylomata Acuminata

Warts

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

All Drugs and Chemicals

Vaccines

V502

Medical Monitor

This study is to evaluate an investigational vaccine with the following objectives: (1) To demonstrate prevention of cervical, vulvar, and vaginal cancers and related precancers, external genital lesions, and persistent infection caused by the HPV types in the study vaccine, (2) To demonstrate that the vaccine is well-tolerated in women, (3) To evaluate vaccine immune responses in women.

This is an early phase trial and some specific protocol information is proprietary and not publicly available at this time. (Full information is available to trial participants).

Broad Spectrum HPV Vaccine Tolerability, Immunogenicity, and Efficacy Study (V502-003)

Proprietary Information - Exploratory (Non-Confirmatory) Trial

Merck Sharp & Dohme LLC

Rare Diseases

Squamous Intraepithelial Lesions of the Cervix

Carcinoma

Carcinoma, Squamous Cell

Carcinoma in Situ

Uterine Cervical Dysplasia

Precancerous Conditions

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Cervical Intraepithelial Neoplasia

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Aldesleukin

Immunomodulating Agents

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at the MTD) + aldesleukin

Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

E6 T Cell Receptor (TCR)

Scott Norberg, DO

Background:

Vulvar high-grade squamous intraepithelial lesion (HSIL) is caused by infection of the vulva with human papillomavirus (HPV). In a small percentage of cases, vulvar HSIL can turn into cancer. The risk of cancer can be reduced by treating HSIL. A personalized immune treatment might rid the body of HPV infection and thereby cure vulvar HSIL. The immune treatment in this study is called T cell therapy. The cells are E6 T Cell Receptor (TCR) T cells. Participants will also get aldesleukin (IL-2) to help the cells last longer.

Objective:

To find a safe dose of E6 TCR T cells combined with aldesleukin to use in people with vulvar HSIL.

Eligibility:

Design:

Participants will be screened with:

Physical exam

Medical history

Blood, lab, and pregnancy tests

Heart tests

Chest x-ray

Sample of tissue taken from the vulva (biopsy).

Participants will have leukapheresis. Blood will be removed by a needle in one arm. A machine removes white blood cells from the blood. The rest of the blood is returned by needle in the other arm. The white blood cells will be changed into E6 TCR T cells and grown in a lab. About 3 weeks later, participants will be admitted to the hospital for about 5 days. They will get the cells through a tube placed in a vein. They will get IL-2 the same way. Participants will recover 1-3 days in the hospital. They will be monitored closely. They will have blood and lab tests. Participants will have follow-up visits with lab tests and a physical exam every few months for 5 years. At some visits they will also have leukapheresis, blood tests, or vulvar biopsy.

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 an HPV-16 E6-specific

T cell receptor (E6 TCR T cells).

Objective:

-Determine the safety of E6 TCR T cells for 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 and less than or equal to 65 years old.
* Eastern Oncology Cooperative Group Performance Score of 0 or 1.

Design:

* This is a phase I clinical trial with a 3+3 dose escalation design.
* Subjects will receive E6 TCR T cells followed by up to two doses of aldesleukin 720,000 IU/kg intravenous (IV).
* No conditioning regimen will be given, aldesleukin will be capped at a maximum of two doses, and E6 TCR T cell dosing will begin at dose level -1 from the previously determined safe dose.

Immunotherapy With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

A Phase I Study of Immunotherapy With E6 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

DLT is defined as all treatment related Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL) and greater adverse events occurring within 30 days of the cell infusion with the exception of the following expected transient effects of aldesleukin. Grade 3 fever or chills responsive to symptomatic treatment that resolve to ≤ grade 2 in 48 hours. Grade 3 hypotension or oliguria responsive to ≤ 1.5L of intravenous fluid boluses in 24 hours that resolves to ≤ grade 2 in 48 hours. Grade 3 dyspnea/hypoxia that improves to ≤ grade 2 or less with supplemental oxygen and resolves to ≤ grade 2 without supplemental oxygen in 48 hours. Grade 3 creatinine or electrolyte abnormalities that resolve to ≤ grade 2 in 48 hours.

MTD is defined as the highest dose at which a maximum of 1 of 6 participants has a dose limiting toxicity (DLT). A DLT is defined as all treatment related Grade 3 (i.e. severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL)) and greater adverse events occurring within 30 days of the cell infusion with the exception of Grade 3 fever or chills responsive to symptomatic treatment that resolve to ≤ grade 2 in 48 hours. Grade 3 hypotension or oliguria responsive to ≤ 1.5L of intravenous fluid boluses in 24 hours that resolves to ≤ grade 2 in 48 hours. Grade 3 dyspnea/hypoxia that improves to ≤ grade 2 or less with supplemental oxygen and resolves to ≤ grade 2 without supplemental oxygen in 48 hours. Grade 3 creatinine or electrolyte abnormalities that resolve to ≤ grade 2 in 48 hours.

Complete Response (CR) is disappearance of all target lesions. No appearance of new lesions. Partial Response (PR) is a ≥50% decrease in the sum of the product of the longest perpendicular diameters of target lesions, taking as reference the baseline measurements. No appearance of new lesions. No increase of greater than 25% of index lesion. Progressive disease is a ≥25% increase in the sum of the product of the longest perpendicular diameters of target lesions, taking as reference the smallest product on study (this includes the baseline product if that is the smallest on study). In addition to the relative increase of 25%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression. Non-CR/Non-PD is neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest product of diameters while on study.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

National Cancer Institute (NCI)

Principal Investigator

One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Dose Level -1: 0.7 x 10^10 Transduced T Cells

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Maximum Tolerated Dose (MTD) of E6 T Cell Receptor (TCR) T Cells for the Treatment of Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL)

Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL)

Number of Participants With Serious and Non-Serious Adverse Events

The protocol was amended to exclude Grade 3 or higher white blood cell count decreased/lymphocyte count decreased that resolved to less than Grade 2 in 72 hours. This was done since transient lymphopenia is not a clinically significant event.

Number of Grade 4 Lymphocyte Count Decreased Dose Limiting Toxicities (DLT)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Broad Spectrum HPV Vaccine Tolerability, Immunogenicity, and Efficacy Study (V502-003)	NCT00365443	Cervical Cancer Condylomata Acu...	V502	16 Years - 26 Years	Merck Sharp & Dohme LLC
Immunotherapy With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions	NCT03197025	Human Papilloma... HPV-16 High Grade Squa...	Aldesleukin E6 T Cell Recep...	18 Years - 65 Years	National Institutes of Health Clinical Center (CC)
Broad Spectrum HPV Vaccine Tolerability, Immunogenicity, and Efficacy Study (V502-003)	NCT00365443	Cervical Cancer Condylomata Acu...	V502	16 Years - 26 Years	Merck Sharp & Dohme LLC
Broad Spectrum HPV Vaccine Tolerability, Immunogenicity, and Efficacy Study (V502-003)	NCT00365443	Cervical Cancer Condylomata Acu...	V502	16 Years - 26 Years	Merck Sharp & Dohme LLC
Immunotherapy With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions	NCT03197025	Human Papilloma... HPV-16 High Grade Squa...	Aldesleukin E6 T Cell Recep...	18 Years - 65 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for premalignancy