Individual Patient TCR-Transduced PBL(NCI)

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.

Background:
A person s tumor is studied for mutations. When cells are found that can attack the mutation in a person s tumor, the genes from those cells are studied to find the parts that make the attack possible. White blood cells are then taken from the person s body, and the gene transfer occurs in a laboratory. A type of virus is used to transfer the genes that make those white blood cells able to attack the mutation in the tumor. The gene transfer therapy is the return of those white blood cells back to the person.
Objective:
To see if gene transfer therapy of white blood cells can shrink tumors.
Eligibility:
People with certain metastatic cancer for which standard treatments have not worked.
Design:
Participants may complete screening under another protocol. Screening includes:
* Getting tumor cells from a previous procedure
* Medical history
* Physical exam
* Scans
* Blood, urine, heart, and lung tests
The study has 8 stages:
1. Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm.
2. Care at home over approximately 12 weeks.
3. Stopping therapy for 4-6 weeks while their cells are changed in a lab.
4. Hospital stay approximately 3-4 weeks for treatment. An IV catheter will be placed in the chest to administer drugs.
5. Patients on Arm 2 of the study will receive the first dose of pembrolizumab while in the hospital. Three additional doses will be given after the cell infusion 3 weeks apart.
6. Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer.
7. Recover in the hospital for 1-2 weeks. Participants will get drugs and have blood and urine tests.
8. Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined.
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