T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers

Summary

Background:

The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. Researchers want to test this on human papilloma virus (HPV)-associated cancers.

Objective:

\- The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (Anti-HPV E6) can shrink tumors associated with HPV and test the toxicity of this treatment.

Eligibility:

\- Adults age 18-66 with an HPV-16-associated cancer.

Design:

* Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed
* Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti HPV E6 cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}
* Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti HPV E6 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.

Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Conditions

• Vaginal Cancer
• Cervical Cancer
• Anal Cancer
• Penile Cancer
• Oropharyngeal Cancer

Interventions

DRUG

Fludarabine

Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.

DRUG

Cyclophosphamide

Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days

BIOLOGICAL

E6 TCR

On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)

DRUG

Aldesleukin

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Christian S Hinrichs, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-10-14

Primary Completion

2016-06-28

Completion

2016-06-28

FDA Drug

Yes

Countries

• United States

Study Locations