Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated or Viral Neoantigens in a Patient With Metastatic Cancer Plus the Administration of Pembrolizumab

Summary

Background:

A cancer treatment has been developed called "gene transfer" or "gene therapy." It involves taking white blood cells from a person (called apheresis), genetically modifying the cells in a lab to recognize cancer, and then giving the cells back to the person. Researchers want to see if this treatment can help people with metastatic squamous cell anal cancer.

Objective:

To see if treating cancer with a person s own white blood cells that have been genetically modified can cause tumors to shrink.

Eligibility:

People who have metastatic squamous cell anal cancer for which standard treatments have not worked.

Design:

Participants will have had a tumor biopsy and apheresis to collect white blood cells under a separate protocol.

Participants will stay at the hospital for 3 to 4 weeks. They will have an intravenous (IV) catheter placed in a large vein in the upper chest.

Participants will get chemotherapy drugs (fludarabine and cyclophosphamide), the cell infusion, and aldesleukin through the IV. Pembrolizumab is given before and for three doses given every three weeks after the cell infusion. Aldesleukin will help the cells grow.

Participants will take an antibiotic, antiviral, and antifungal by mouth. They will get an injection of filgrastim. It will stimulate the formation of white blood cells.

Participants will have blood and urine tests. They will have physical exams. Their symptoms will be reviewed. They will have imaging scans.

About 6 and 12 weeks after they finish treatment, participants will have safety follow-up visits. These visits will take 1 to 2 days.

Participants will return to the Clinical Center every 3 to 6 months for 3 years, and then as determined by their doctor. They will be followed long term for up to 15 years on a separate study.

Conditions

• Metastatic HPV-16 Positive Squamous Cell Anal Cancer

Interventions

DRUG

Cyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg /day over 1 hour x 2 days.

DRUG

Fludarabine

Days -7 to -3: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days.

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 4 days (maximum 10 doses).

DRUG

Pembrolizumab (KEYTRUDA(R))

Pembrolizumab 2 mg /kg IV over approximately 30 minutes on Days -2, 21, 42, and 63.

BIOLOGICAL

Individual Patient TCR-Transduced PBL

Day 0: Cells will be infused at a dose not to exceed 1.5e11 in 400 mL intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven A Rosenberg, 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

2021-01-27

Primary Completion

2021-01-27

Completion

2021-01-27

FDA Drug

Yes

Countries

• United States

Study Locations