Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Anti-gp100:154-162 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, human leukocyte antigen (HLA-A\*0201) derived from the gp100 protein. A retroviral vector was constructed that can deliver the TCR to cells.
* This gene-engineered cell is over 10 times more reactive with melanoma cells than is the melanoma antigen recognized by T-cells (MART-1) TCR that resulted in tumor shrinkage for two patients with metastatic melanoma.

Objectives:

* To determine whether an anti-melanoma protein receptor 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-gp100 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-gp100. Patients receive an IV infusion of the treated cells containing anti-gp100 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 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

• Skin Cancer
• Melanoma

Interventions

DRUG

fludarabine phosphate

25 mg/m\^2/day intravenous piggy back over 30 minutes for 5 days.

DRUG

cyclophosphamide

60 mg/kg/day x 2 days intravenous

BIOLOGICAL

aldesleukin

720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).

BIOLOGICAL

autologous anti-gp 100:154-162 T-cell receptor gene-engineered tumor infiltrating lymphocytes

Patients will receive a minimum of approximately 5 X 10\^8 cells and up to 3 x10\^11 anti-gp100:154-162 TCR engineered TIL . The cells are infused intravenously over 20-30 minutes.

BIOLOGICAL

autologous anti-gp 100:154-162 T-cell receptor gene-engineered peripheral blood lymphocytes

Patients will receive a minimum of approximately 5 X 10\^8 cells and up to 3 x10\^11 anti-gp100:154-162 TCR engineered PBL. The cells are infused intravenously over 20-30 minutes.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

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