Anti-MART-1 F5 Lymphocytes to Treat High-Risk Melanoma Patients

Summary

Background:

* Melanoma antigen recognized by T cells (MART-1) is a gene that is present in melanoma cells.
* This study tests an experimental treatment that uses the patient's own lymphocytes (type of white blood cell), which are specially selected and genetically modified with a gene called anti-MART-1 transduced cells (F5) to target and destroy their tumor. Some of the cells are given as an infusion and others are given as a vaccine.
* The anti-MART-1 F5 cells are currently being studied in other patients in combination with chemotherapy and IL-2 (aldesleukin) therapy.

Objectives:

-To determine if the anti-MART-1 F5 treatment can improve the immune system's ability to shrink tumors and to prevent melanoma from recurring.

Eligibility:

* Patients 18 years of age and older whose melanoma has been removed and are currently disease-free, but who are at risk for recurrence.
* Patients who do not have ocular or mucosal melanoma.
* Patients with tissue type human leukocyte antigens (HLA-A)\*0201).

Design:

* Workup: Patients have scans, x-rays, laboratory tests, other tests as needed and leukapheresis, a procedure for collecting white cells to modify in the laboratory and later reinfuse into the patient.
* Patients are assigned to one of four study groups:

* Group 1 receives anti-MART-1 F5 cells by 30-minute infusion through a vein on day 0.
* Group 2 receives anti-MART-1 F5 cells on day 0 followed by injections of MART-1 vaccine, which contains MART-1 and an oil-based liquid called Montanide ISA-51 VG. The vaccine is repeated on day 30.
* Group 3 receives anti-MART-1 F5 cells on day 0 followed by injections of low-dose IL-2 for 5 days (days 0-4).
* Group 4 receives anti-MART-1 F5 cells on day 0 followed by MART-1 vaccine and low-dose IL-2 for 5 days. The vaccine is repeated on day 30.
* Recovery: Patients are monitored closely and given medicines to prevent or treat any side effects of therapy.
* Leukapheresis: Patients undergo leukapheresis at 1 and 3 months after therapy to collect cells to examine the effects of the treatment on the immune system.
* Follow-up: Patients return to National Institutes of Health (NIH) 35 days after completing treatment and then at 3 months and every 6 months thereafter for evaluation with a physical examination, review of side effects, laboratory tests and scans. They have blood tests at 3, 6 and 12 months after treatment and then once a year after that. A biopsy may be requested after treatment ends to examine the effects of treatment on the immune system. All patients return to NIH for a physical examination once a year for 5 years and then complete a follow-up questionnaire for another 10 years.

Conditions

• Melanoma

Interventions

BIOLOGICAL

ALVAC-MART-1 vaccine

Given subcutaneously

BIOLOGICAL

MART-1:26-35(27L) peptide vaccine

Given subcutaneously

BIOLOGICAL

Aldesleukin

Given subcutaneously

BIOLOGICAL

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

Given intravenously (IV)

BIOLOGICAL

incomplete Freund's adjuvant

Given subcutaneously

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

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

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-06-30

Primary Completion

2012-11-30

Completion

2012-11-30

Countries

• United States

Study Locations