Finding studies
Finding studies
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Lead
National Cancer Institute (NCI)
Background: * Natural killer (NK) cells are large granular lymphocytes that are critical effector cells in the early innate immune response to pathogens and cancer. * Previous and current clinical investigations have clearly demonstrated that T lymphocytes can mediate the regression of metastatic melanoma. However, not all patients with cancer are eligible for this type of immunotherapy either because resectable tumor is not available, the TIL do not expand sufficiently, or the tumor infiltrating lymphocytes (TIL) that do proliferate do not exhibit sufficient tumor specific reactivity. * We have recently developed techniques for the in vitro isolation and expansion of anti-tumor NK cells to levels suitable for the treatment of cancer patients and are proposing in this protocol to evaluate therapy using these NK cells. * In Surgery Branch pre-clinical experiments, we evaluated lysis of fresh melanoma cell digests, melanoma cell lines, renal cell carcinoma (RCC) lines, and normal peripheral blood mononuclear cells (PBMCs) by NK cells from several patients and demonstrated that NK cells could lyse some fresh melanoma digests, as well as melanoma cell lines and renal cell cancer (RCC) lines, while sparing normal allogeneic and autologous PBMCs. Objectives: * Determine the ability of the administration of autologous natural killer (NK) cells plus aldesleukin (IL-2) following a non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma or kidney cancer. * Determine the rate of repopulation of the natural killer cells in treated patients. * Determine the toxicity of this treatment regimen. Eligibility: * Patients, 18 years of age or older with metastatic melanoma or metastatic kidney cancer who have previously received high dose IL-2, with an Eastern Cooperative Oncology Group (ECOG) of 0 or 1. * Patients may not have any active systemic infections, coagulations disorders, major medical illnesses of the cardiovascular, respiratory or immune systems or any form of autoimmune disease or immunodeficiency. Patients must be eligible to receive high-dose IL-2. Design: * Patients will undergo apheresis on 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols) to obtain cells for generation of autologous natural killer cells. * All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide (60 mg/kg/day IV) on days -8 and -7 and fludarabine (25 mg/m\^2/day IV) on days -6 through -2. * On day 0 patients will receive the infusion of autologous natural killer lymphocytes and then begin the first cycle of high-dose IL-2 (720,000 IU/kg IV every 8 hours for up to 15 doses). A second cycle of IL-2 will be administered approximately 14 days later. * Clinical and Immunologic response will be evaluated about 4 to 6 weeks after the second cycle of IL-2. -Using a small optimal Phase II design, two cohorts of patients, initially 16 in each cohort, will be enrolled, and if at least one of the first 16 patients has a clinical response (partial response (PR) or complete response (CR)), accrual will continue to 29 patients, targeting a 15% goal for objective response.
Age
18–any
Sex
ALL
Healthy volunteers
Not accepted
