Non-Viral TCR Gene Therapy

Summary

Background:

A person s white blood cells can be modified in a lab to recognize certain changes in their tumor. Many of these cells are collected from the person, modified, then given back to the person. This may help treat some cancers.

Objective:

To learn if a person s white blood cells modified with T-cell receptors can cause solid tumors to shrink.

Eligibility:

People ages 18-70 who have cancer of the gastrointestinal tract, genitourinary tract, ovary, breast, or lung that has spread, or who have glioblastoma.

Design:

Participants will be screened and have their cells prepared for treatment in another protocol.

Participants will be hospitalized one week before treatment. They will stay approximately 3 - 4 weeks after treatment.

Participants will get the modified white blood cells and chemotherapy through an IV catheter, which is a small plastic tube inserted in a vein.

Participants will take drugs by mouth to prevent infection. They will receive filgrastim as a shot or injection under the skin.

Participants will have tests before, during, and after treatment:

Heart, blood, and urine tests

Chest X-ray

Physical exam

Scans: They will lie in a machine that takes pictures of the body.

Possible apheresis: The participant s blood is removed through a needle in an arm. The blood goes through a machine that removes the white blood cells. The rest of the blood is returned through a needle in the other arm.

Participants will have visits about 6 and 12 weeks after treatment. If they are responding to treatment, they will then have visits every 3-6 months for 3 years. Then they will join another study and be followed about 12 more years.

Conditions

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

Interventions

DRUG

Fludarabine

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

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

Aldesleukin

Aldesleukin 720,000 IU/kg or 72,000 IU/kg (based on total body weight) IV over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 10 doses).

BIOLOGICAL

Sleeping Beauty Transposed PBL

Day 0: Cells are to be infused at a dose not to exceed 1.5e11 in 400 mL intravenously on the Patient Care Unit over 20-30 minutes or as clinically determined by an investigator for patient safety (between 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

2024-03-08

Primary Completion

2024-03-08

Completion

2024-03-08

FDA Drug

Yes

Countries

• United States

Study Locations