Anti-MART-1 F5 Cells Plus ALVAC MART-1 Vaccine to Treat Advanced Melanoma

Summary

Background:

* Melanoma antigen recognized by T-cells (MART)-1 is a protein present in melanoma cells.
* An experimental procedure developed for treating patients with melanoma uses the anti-MART-1 F5 gene and a type of virus to make special cells called anti-MART-1 F5 cells that are designed to destroy the patient's tumor. These cells are created in the laboratory using the patient's own tumor cells or blood cells.
* The treatment procedure also uses a vaccine called plaque purified canarypox vector (ALVAC) MART-1, made from a virus that ordinarily infects canaries and is modified to carry a copy of the MART-1 gene. The virus cannot reproduce in mammals, so it cannot cause disease in humans. When the vaccine is injected into a patient, it stimulates cells in the immune system that may increase the efficiency of the anti-MART-1 F5 cells.

Objectives:

-To evaluate the safety and effectiveness of anti-MART-1 F5 and the ALVAC vaccine in treating patients with advanced melanoma.

Eligibility:

-Patients 18 years of age with metastatic melanoma for whom standard treatments have not been effective.

Design:

* Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells for laboratory treatment.
* Patients have 7 days of chemotherapy to prepare the immune system for receiving the anti-MART-1 F5.
* Patients receive the ALVAC vaccine, anti-MART-1 F5 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti-MART-1 F5 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of anti-MART-1 F5 cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days after the cell infusion for a maximum of 15 doses.
* After hospital discharge, patients return to the clinic for periodic follow-up with a physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.

Conditions

• Metastatic Melanoma
• Skin Cancer

Interventions

BIOLOGICAL

autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes

ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10\^7 CCID50 (with a range of approximately 10\^6,4 to 10\^7,9/mL) of the MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10\^7 CCID50/2 mL). This will be repeated on day 14.

BIOLOGICAL

ALVAC MART-1 Vaccine

ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10\^7 CCID50 (with a range of approximately 10\^6,4 to 10\^7,9/mL) of the MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10\^7 CCID50/2 mL). This will be repeated on day 14.

BIOLOGICAL

aldesleukin

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

DRUG

cyclophosphamide

60 mg/kg day x 2 days intravenous in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg day x 2 days over 1 hour

DRUG

fludarabine phosphate

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

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

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-01-31

Primary Completion

2011-03-31

Completion

2011-03-31

Countries

• United States

Study Locations