This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting
chemotherapy in combination with adoptive immunotherapy in patients with metastatic
melanoma. The
chemotherapy-conditioning schedule that induced transient
lymphopenia consisted of
cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by
fludarabine (25 mg/m(2) per day for 5 days).
Immunotherapy for all patients consisted of in vitro expanded,
tumor-reactive, autologous T-cell clones selected for high avidity recognition of
melanoma antigens. Cohorts of three to six patients each received either no
interleukin (IL)-2, low-dose
IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose
IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included
neutropenia and
thrombocytopenia that resolved in all patients. High dose intravenous
IL-2 was better tolerated by patients after
chemotherapy than during previous
immunotherapy cycles without
chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and
IL-2 in patients with metastatic
melanoma.