Protocol Number: 04-C-0251

Title:

A Study in Metastatic Melanoma Using a Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 TCR-Gene Engineered Lymphocytes and Subsequent Peptide Immunization

Number:

04-C-0251

Summary:

This study will examine the safety and effectiveness of gene therapy for creating special tumor-fighting cells to treat patients with metastatic melanoma (melanoma that has spread beyond the primary tumor site). An anti-melanoma gene is inserted into immune cells collected from the patient's blood or tumor and the gene-modified cells are grown in culture and then given back to the patient.

Patients 18 years of age and older with metastatic melanoma who have been treated with the growth factor interleukin-2 (IL-2) and have progressive disease may be eligible for this study. Patients must have tissue type HLA-A*0201. Candidates are screened with a physical examination, eye examination, electrocardiogram (EKG), blood and urine tests, scans, and x-rays to evaluate the tumor. Some patients may have a cardiac stress test or lung function test. Participants undergo the following procedures:

- Tumor biopsy and cell culture: A small area of skin is numbed and a piece of tumor is removed with a needle or a small incision. The tumor cells are grown in the laboratory for about 40 days. If the cells do not grow well, blood is collected through leukapheresis to try to grow lymphoctyes. For leukapheresis, whole blood is drawn from a needle in an arm vein and circulated through a machine that separates it into its components. The white cells are removed and the plasma and red cells are given back to the patient through a vein in the other arm.

- MART-1 gene insertion into cells: While the cells are growing in culture, anti-melanoma protein genes called MART-1 are inserted into them using a virus that has been made incapable of causing infection.

- Chemotherapy: Patients receive two immune-suppressing drugs, cyclophosphamide and fludarabine, through a catheter (flexible plastic tube) in a vein in the arm, upper chest, or neck. The cyclophosphamide is given over 1 hour for 2 days; then the fludarabine is given for 30 minutes for 5 days. The drugs are not intended to treat the tumor, but to see if the immune suppression improves the functioning of the gene-modified white cells.

- After chemotherapy, patients receive two injections of a vaccine to increase the immune response to the tumor. The vaccine consists of pieces of the same MART-1 protein that the cultured cells were modified to react with, along with an adjuvant called Montanide ISA-51 to boost the immune response to the protein. The injections are given the morning of the cell infusion (see below), then every day for a total of 5 days, and then weekly for 3 more weeks.

- Cell infusion: The gene-modified cells are given through the catheter over 30 minutes the day after the last dose of chemotherapy. Within 24 hours after the cell infusion, high-dose IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days. Patients are monitored closely for side effects and are given medicines as needed to treat and prevent as many side effects as possible.

Patients may be asked to undergo a tumor or lymph node biopsy after treatment to look at the effects of treatment on the tumor immune cells. Patients whose tumor remains stable or shrinks may have one additional treatment. Patients return to NIH for a 2-day follow-up evaluation 4-6 weeks after each treatment and then annually for physical examinations.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Maximum Tolerated Dose

In Vivo Survival

Toxicity Profile

Clinical Response

Adoptive Cell Therapy

Recruitment Keyword(s):

Metastatic Melanoma

Condition(s):

Melanoma

Metastases

Investigational Drug(s):

MSGV1AIB Periperhal Blood Lymphocytes

MSGV1AIB Tumor-Infiltration Lymphocytes

MART- 1: 26 35(27L)

IL-2

Montanide ISA 51 VG

Investigational Device(s):

None

Interventions:

Drug: GCsamAPB(anti-MART-1 TCR) retroviral vector-transduced autologous tumor infiltra

Drug: GCsamAPB (anti-MART-1 TCR) retroviral vector-transduced autologous peripheral bl

Drug: MART- 1: 26 35(27L)

Drug: Montanide ISA 51

Drug: Montanide ISA 51 VG

Drug: MART-1:26-35(27L) Peptide

Drug: MSGV1AIB Periperhal Blood Lymphocytes

Drug: MSGV1AIB Tumor-Infiltration Lymphocytes

Drug: IL-2

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature. 2001 May 17;411(6835):380-4. Review.

Schwartzentruber DJ, Topalian SL, Mancini M, Rosenberg SA. Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IFN-gamma by human tumor-infiltrating lymphocytes after autologous tumor stimulation. J Immunol. 1991 May 15;146(10):3674-81.

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009