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 (IL-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
growth colony stimulating factor (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.
Patients with metastatic melanoma who are human immunodeficiency virus (HIV) and Hepatitis B
negative and who have previously progressed after receiving standard therapy will receive a
nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide
and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive
with shared antigens on their tumors. This study will evaluate the toxicity, immunologic
effects and potential therapeutic role of this treatment.
- INCLUSION CRITERIA
- Patients must have evaluable metastatic melanoma that is refractory to standard
- 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 Eastern Cooperative Oncology Group (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 alanine aminotransferase (ALT)/aspartate aminotransferase (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 human immunodeficiency virus (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
- Seronegative for hepatitis B antigen.
- Patients to receive high dose interleukin 2 (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.