Protocol Number: 99-C-0158

Title:

Treatment of Patients with Metastatic Melanoma Using Cloned Lymphocytes Following the Administration of a Non-Myeloablative but Lymphocyte Depleting Regimen

Number:

99-C-0158

Summary:

This experiment will test the safety and effectiveness of a treatment for melanoma in which certain lymphocytes (a type of white blood cell) are taken from the patient, grown in the laboratory, and returned after the patient's immune system has been weakened with immune-suppressing drugs. Some patients will also receive interleukin-2, a drug that may enhance the activity of the re-infused lymphocytes.

Patients with metastatic melanoma (melanoma whose tumor has spread) who have been treated unsuccessfully with gp100 vaccination may participate in this study. They will undergo apheresis or a tumor biopsy, or both, to collect lymphocytes. In apheresis, whole blood is drawn through a needle in the arm. A machine separates the blood components and removes the white cells. The rest of the blood is returned to the donor through a needle in the other arm. A biopsy is a surgical procedure to remove a small piece of tumor tissue.

Several weeks before the lymphocytes are collected, patients will receive injections of G-CSF every day for five days. This drug stimulates white cell production, permitting as many cells as possible to be obtained during collection. The lymphocytes will then be grown in larger numbers in the laboratory.

Seven days before the cells are re-infused, the patient is admitted to the hospital and a catheter (small tube) is placed in a large vein in the chest or neck. Two drugs, cyclophosphamide and fludarabine, are given through the tube. These drugs suppress the immune system so that it will not interfere with the work of the reinfused lymphocytes. The lymphocytes are then injected through the catheter over a 30-minute period. After the infusion, patients who receive IL-2 will be given the drug in a high dose over a 15-minute period every eight hours for up to five days. Patients whose condition does not permit high-dose IL-2, such as those with a heart condition or lung problem, may receive a low-dose regimen, with the drug given as a shot under the skin of the thigh or abdomen for five days followed by a 2-day break, continuing for a total of six weeks. These patients receive a higher dose the first week and then half that dose the next five weeks.

Blood and tissue samples will be taken before and during the study to evaluate the size of the tumor and assess treatment. If, 3-5 weeks after therapy is completed, the patient's tumor has stabilized or shrunk, the entire treatment, except for chemotherapy, may be repeated two more times.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

Patients must have evaluable metastatic melanoma.

Age greater than or equal to 16 years.

Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.

Clinical performance status of ECOG 0, 1 at entry to the trial and at the time of chemotherapy induction.

Absolute neutrophil count greater than 1000/mm(3).

Platelet count greater than 100,000/mm(3).

Hemoglobin greater than 8.0 g/dl.

Serum ALT/AST less than two times the upper limit of normal.

Serum creatinine less than or equal to 1.6 mg/dl.

Total bilirubin less than or equal to 1.6 mg/dl, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

More than four weeks must have elapsed since any prior therapy at the time the patient receives the preparative regimen.

Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

Life expectancy of greater than three months.

No steroid therapy required.

Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

Seronegative for hepatitis B antigen.

Patients to receive high dose IL-2 must have no active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system.

Patients who will receive high dose IL-2 as part of the phase I portion of this study or who will be randomized must be eligible to receive high dose IL-2.

Any patient receiving IL-2 must sign a durable power of attorney.

Special Instructions:

Currently Not Provided

Keywords:

Immunotherapy

Adoptive Transfer

IL-2

Toxicity

Clinical Response

Recruitment Keyword(s):

Breast Cancer

Condition(s):

Melanoma

Neoplasm Metastasis

Investigational Drug(s):

gp100:209-217 (210M)

Montanide ISA-51

IL-2

Retroviral Vector PG13/LNC8

Orthoclone OKT3

MART-1:26-35(27L)

Investigational Device(s):

None

Intervention(s):

Drug: gp100:209-217 (210M)

Drug: Montanide ISA-51

Drug: IL-2

Drug: Retroviral Vector PG13/LNC8

Drug: Orthoclone OKT3

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

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

The immunotherapy and gene therapy of cancer

Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IFN-gamma by human tumor-infiltrating lymphocytes after autologous tumor stimulation

Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor

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