E7 TCR T Cells for Human Papillomavirus-Associated Cancers
- Conditions
- Cervical Intraepithelial NeoplasiaVulvar NeoplasmsPapillomavirus InfectionsCarcinoma In SituVulvar Diseases
- Interventions
- Registration Number
- NCT02858310
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have a HPV protein called E7 inside of their cells. In this new therapy, researchers take a person s blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 TCR cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people.
Objective:
To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients.
Eligibility:
Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal.
Design:
Participants will list all their medicines.
Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein.
Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.
The cells will be changed in the lab.
Participants will stay in the hospital. Over several days, they will get:
Chemotherapy drugs
E7 TCR cells
Shots or injections to stimulate the cells
Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests.
Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays.
Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis.
Participants will be followed for 15 years.
- Detailed Description
Background:
* Metastatic or refractory/recurrent human papillomavirus (HPV)-16+ cancers (cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers) are incurable and poorly palliated by standard therapies.
* HPV-16+ cancers constitutively express the HPV-16 E7 oncoprotein, which is absent from healthy human tissues.
* Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers.
* T cells genetically engineered with a TCR targeting HPV-16 E7 (E7 TCR) display specific reactivity against HLA-A2+, HPV-16+ target cells.
Objectives:
Phase I Primary Objective
\- To determine a safe dose for E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers.
Phase II Primary Objective
-To determine safety and efficacy of E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers.
Eligibility:
* Patients greater than or equal to 18 years old with metastatic or refractory/recurrent HPV-16+ cancer.
* Prior first line systemic therapy is required unless the patient declines standard treatment.
* Patients must be HLA-A\*02:01-positive.
Design:
* This is a phase I/II clinical trial that will test the safety and efficacy of E7 TCR cells.
* All patients will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of E7 TCR cells. Cell infusion will be followed by high-dose aldesleukin.
* Re-enrollment will be allowed for a small number of subjects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 219
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1: Phase I E7 TCR cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 TCR Cells at escalating doses, followed by aldesleukin Arm 1: Phase I Cyclophosphamide Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 TCR Cells at escalating doses, followed by aldesleukin Arm 1: Phase I Fludarabine Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 TCR Cells at escalating doses, followed by aldesleukin Arm 2: Phase II Fludarabine 1 x 10 e11 E7 Cells that was determined in Phase I + aldesleukin Arm 2: Phase II E7 TCR cells 1 x 10 e11 E7 Cells that was determined in Phase I + aldesleukin Arm 2: Phase II Cyclophosphamide 1 x 10 e11 E7 Cells that was determined in Phase I + aldesleukin Arm 1: Phase I Aldesleukin Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 TCR Cells at escalating doses, followed by aldesleukin Arm 2: Phase II Aldesleukin 1 x 10 e11 E7 Cells that was determined in Phase I + aldesleukin
- Primary Outcome Measures
Name Time Method Phase II: Determine safety and effficacy of E7 TCR cells plus aldesleukin At 12 weeks, every 3 months x 3, every 6 months x 5 years, then as per PI discretion thereafter Overall response rate (PR +CR)
Phase I: Determine a safe dose for E7 TCR cells plus aldesleukin 30 days after treatment Number and type of AEs and/or UPs
- Secondary Outcome Measures
Name Time Method To assess progression-free survival at time of last patient's progression time from start of treatment to disease progression or death
Trial Locations
- Locations (2)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
National Institutes of Health Clinical Center🇺🇸Bethesda, Maryland, United StatesFor more information at the NIH Clinical Center contact National Cancer Institute Referral OfficeContact888-624-1937