Protocol Number: 04-C-0181

Title:

Treatment of Patients with Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination

Number:

04-C-0181

Summary:

This study will use genetically engineered lymphocytes (white blood cells) and an experimental vaccine to treat advanced melanoma. Tumor-fighting lymphocytes taken from the patient's blood or tumor are grown in the laboratory and treated with an anti-melanoma protein for later re-infusion into the patient. The protein is inserted into the cells with a virus that has been inactivated so that it cannot cause illness.

Patients 18 years of age and older with metastatic melanoma that does not improve with standard therapy or treatment with high-dose IL-2 and who have tissue type HLA-A*0201 may be eligible for this study. Candidates are screened with a medical history and physical examination, chest x-ray, electrocardiogram, blood and urine tests, and x-rays and scans to the evaluate the extent and size of the tumor.

Participants undergo the following procedures:

- Tumor biopsy: A small piece of tumor is obtained either with a needle or by a small cut in the tumor to collect lymphocytes with good tumor-fighting ability for treatment with the anti-melanoma protein. Alternatively, the cells may be collected by leukapheresis, in which blood is withdrawn through a needle in an arm vein and directed through a catheter into a cell-separating machine. The lymphocytes are removed and the rest of the blood is returned to the body through the same needle.

- G-CSF injections: This growth factor is injected under the skin every day for 5 days before leukapheresis (see below) to stimulate white blood cell production.

- Leukapheresis: Leukapheresis is performed to collect and store blood that may be needed in the rare event that the patient's blood components do not recover after chemotherapy.

- Catheter placement: When the patient is admitted to the Clinical Center for treatment, a catheter (plastic tube) is placed in a vein in the patient's neck or arm for giving chemotherapy and other medicines, infusing the lymphocytes, and collecting blood samples.

- Chemotherapy: A week before the lymphocyte infusion, patients receive a 1-hour infusion of cyclophosphamide for 2 days and then a 15- to 30-minute infusion of fludarabine for 5 days to suppress the immune system and thereby prevent rejection of the infused lymphocytes.

- Vaccine and lymphocyte delivery: Patients receive vaccine shots in the thigh to boost the immune response to the tumor. The vaccine contains a peptide (piece of a protein) produced by melanoma tumors. Two injections every day for five days beginning the morning of the cell infusion and then once a week for three more injections. The lymphocytes are infused through the catheter over 30 minutes the day after the last dose of chemotherapy.

- IL-2: Patients receive IL-2 infusions every 8 hours for up to 5 days after the cell infusion to help keep the cells alive.

Between 4 and 6 weeks after completing the full treatment regimen, patients return to NIH for about 2 days for evaluation. Patients whose tumor has shrunk or remained stable may repeat the treatment one time. Those whose tumors continued to grow are taken off the study and admitted to another protocol or are returned to the care of their local physician. Patients have blood tests done at 1, 3, 6, and 12 months after the infusion and then yearly to look for changes in the virus used to insert the anti-melanoma protein and for changes in the genetically modified lymphocytes.

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):

gp100

MART-1

HLA-A0201

Clinical Response

Toxicity

Recruitment Keyword(s):

Metastatic Melanoma

Melanoma

Condition(s):

Melanoma

Investigational Drug(s):

GCsamAPB (anti-gp 100 TCR) retroviral vector-transduced autologous tumor-infiltr

GCsamAPB (anti-gp100 TCR) retroviral vector transduced autologous peripheral blo

GP100: 209-217 (210M)

IL-2

Montanide

Investigational Device(s):

None

Interventions:

Drug: GCsamAPB (anti-gp 100 TCR) retroviral vector-transduced autologous tumor-infiltr

Drug: GCsamAPB (anti-gp100 TCR) retroviral vector transduced autologous peripheral blo

Drug: GP100: 209-217 (210M)

Drug: IL-2

Drug: Montanide

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.

Topalian SL, Rosenberg SA. Tumor-infiltrating lymphocytes: evidence for specific immune reactions against growing cancers in mice and humans. Important Adv Oncol. 1990;:19-41.

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.

• 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 of Networks and Applications, CC.

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