E7 TCR T Cells for Human Papillomavirus-Associated Cancers

Summary

Background:

Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have an 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 T cell receptor (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.

Conditions

• Papillomavirus Infections
• Cervical Intraepithelial Neoplasia
• Carcinoma In Situ
• Vulvar Neoplasms
• Vulvar Diseases

Interventions

BIOLOGICAL

E7 TCR cells

T cells genetically engineered with a T cell receptor (TCR) targeting human papillomavirus (HPV -16 E7 (E7 TCR) that display specific reactivity against human leukocyte antigen (HLA-A2+, HPV-16+ target cells.

DRUG

Aldesleukin

Following cell infusion, the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 T cell receptor (TCR) cells after infusion.

DRUG

Fludarabine

Part of the non-myeloablative lymphocyte-depleting preparative regimen.

DRUG

Cyclophosphamide

Part of the non-myeloablative lymphocyte-depleting preparative regimen.

DIAGNOSTIC_TEST

EKG

Screening/Baseline. Follow-up (end of treatment).

PROCEDURE

Biopsy

Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.

DIAGNOSTIC_TEST

Chest CT and MRI or PET

Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.

DIAGNOSTIC_TEST

PFT

Screening/Baseline.

DRUG

Granisetron

Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).

DRUG

Ondansetron

Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).

DRUG

Droperidol

Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).

DRUG

Prochlorperazine

Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.

DRUG

Diphenoxylate HCL

Supportive medication for diarrhea. 2.5mg by mouth (po) every(q) 3 hours(h) as needed (prn).

DRUG

Atropine sulfate

Supportive medication for diarrhea. 25mcg by mouth (po) every(q) 3 hours(h) as needed (prn).

DRUG

Codeine sulfate

Supportive medication for diarrhea. 30-60mg by mouth (po) every(q) 4 hours(h) as needed (prn).

DRUG

Loperamide

Supportive medication for diarrhea. 2mg by mouth (po) every(q) 3 hours(h) as needed (prn).

DRUG

Indomethacin

Supportive medication for fever. 50-75mg by mouth (po) every(q) 8 hours(h).

DRUG

Acetaminophen

Supportive medication for fever. 650mg by mouth (po) every 4 hours (q) 4hr.

DRUG

Diphenhydramine HCL

Supportive medication for pruritis. 25-50mg by mouth (po) every 4 hours (q) 4hr as needed (prn).

DRUG

Hydroxyzine HCL

Supportive medication for pruritis. 10-20mg by mouth (po) every 6 hours(h), as needed (prn).

DRUG

Meperidine

Supportive medication for chills. 25-50mg intravenous (IV) every 1 hour (q1hr), as needed (prn).

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Scott M Norberg, D.O. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-01-27

Primary Completion

2025-07-02

Completion

2025-07-02

FDA Drug

Yes

Countries

• United States

Study Locations