Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

Summary

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.

...

Conditions

• Endocrine Tumors
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Breast Cancer
• Gastrointestinal/Genitourinary Cancers
• Neuroendocrine Tumors
• Multiple Myeloma

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). Patients in Cohort 3 may receive 72,000 IU/kg IV.

BIOLOGICAL

Individual Patient TCR-Transduced PBL

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

DRUG

Pembrolizumab (KEYTRUDA(R))

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven A Rosenberg, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

72 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-09-06

Primary Completion

2027-03-23

Completion

2028-03-23

FDA Drug

Yes

Countries

• United States

Study Locations