Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes

Summary

Background:

* Human peripheral blood lymphocytes have been engineered to express a T-cell receptor (TCR) that recognizes a blood type,HLA-A 0201 (human leukocyte antigen) derived from the gp100 protein. A retroviral vector was constructed that can deliver the T-cell receptor (TCR) to cells.
* Patients' cells will be converted into cells able to recognize and fight melanoma tumors.

Objectives:

* To determine whether TCR-engineered lymphocytes can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors.
* To evaluate safety and effectiveness of the treatment.

Eligibility:

* Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site).
* Patient's leukocyte antigen type is HLA-A 0201.

Design:

-Patients undergo the following procedures:

* Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the anti-MART-1 protein is inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.
* Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) over 1 hour for 2 days to suppress the immune system so that the patient's immune cells do not interfere with the treatment.
* Treatment with anti-melanoma antigen recognized by T-cells (MART)-1. Patients receive an intravenous (IV) infusion of the treated cells containing anti-MART-1 protein, followed by infusions of a drug called IL-2 (aldesleukin), which helps boost the effectiveness of the treated white cells.
* Patients are given support medications to prevent complications such as infections.
* Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue).
* Patients are evaluated with laboratory tests and imaging tests, such as CT (computed tomography) scans, 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment.
* Patients have blood tests at 3, 6, and 12 months and then annually for 5 years.

Conditions

• Melanoma
• Skin Cancer

Interventions

BIOLOGICAL

autologous anti-MART-1 F5 T-cell receptor

Autologous anti-MART-1 F5 T-cell receptor gene-engineered tumor infiltrating lymphocytes. A minimum of approximately 5 X 10\^8 cells will be given up to 3x10\^11 anti-MART-1 F5 TCR engineered TIL or PBL.

DRUG

Cyclophosphamide

Day -7 to -5: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml D5W with mesna 15 mg/kg/day X 2 days over 1 hr

DRUG

Fludarabine

Day -5 to 1: Fludarabine 25 mg/m\^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days

BIOLOGICAL

Aldesleukin

Day 0: Cells will be infused intravenously (i.v.). Patients will receive up to 3x10e\^11 (with a minimum of 5x10e\^8 cells) anti-MART-1 F5 TCR engineered TIL or PBL Aldesleukin (based on total body weight) 720,000 IU/kg intravenous (IV) over 15 minute every eight hours beginning within 24 hours of cell infusion

BIOLOGICAL

autologous anti-MART-1 F5 T-cell receptor gene-engineered tumor infiltrating lymphocytes

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven Rosenberg, M.D. · National Cancer Institute, National Institutes of Health

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-06-30

Primary Completion

2011-07-31

Completion

2012-07-31

Countries

• United States

Study Locations