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 metastatic 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 through a needle in the other arm. A biopsy is a surgical procedure to remove a small piece of tumor tissue. We will find the best cells to fight the melanoma from cells obtained from the pheresis or biopsy. We will take these and grow them in larger numbers in the laboratory. These are called "cloned cells" because we grow a lot of cells that are exactly like the best melanoma fighting cells we started with.

Several weeks before we weaken the immune system and give the "cloned cells", additional lymphocytes are collected after patients 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. These white cells will be frozen in the laboratory and will only be given back to the patient if their immune system does not completely recover from the chemotherapy drugs used to suppress the immune system.

Seven days before the "cloned 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 given through the catheter over a 30-minute period. After the infusion, patients who receive IL-2 will be given the drug over a 15-minute period every 8 hours for up to 5 days. Fourteen to 21 days after this, the patient will be given a second infusion of "cloned cells".

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

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

Patients must have evaluable metastatic melanoma that is refractory to standard therapy.

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 doseIL-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 Keywords:

Breast Cancer

Conditions:

Melanoma

Neoplasm Metastasis

Investigational Drug(s):

gp100:209-217 (210M)

Montanide ISA-51

IL-2

Retroviral Vector PG13/LNC8

OKT3

MART-1:26-35(27L)

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

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

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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Bethesda, Maryland 20892. Last update: 10/15/2004