RATIONALE: Biological therapies, such as therapeutic autologous lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin may be an effective treatment for melanoma. PURPOSE: This phase I trial is studying the side effects of giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin in treating patients with stage IV melanoma
PRIMARY OBJECTIVES: I. To assess the safety and toxicity of cellular adoptive immunotherapy in melanoma patients receiving autologous CD8+ antigen-specific T cell clones following cyclophosphamide conditioning and post-infusion IL-2. II. To assess the duration of in vivo persistence of adoptively transferred CD8+ T cell clones. SECONDARY OBJECTIVES: I. Evaluate the antitumor effect of adoptively transferred CD8+ antigenspecific cytotoxic t lymphocytes (CTL) clones following cyclophosphamide conditioning and post-infusion IL-2. OUTLINE: Patients are assigned 1of 2 treatment cohorts. All patients receive high-dose cyclophosphamide intravenously (IV) on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T lymphocyte clones IV over 30-60 minutes on day 0. COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin subcutaneously (SC) twice daily on days 0-14. COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and every 3 months thereafter for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Given IV
Given IV
Given IV or SC
Correlative studies
Optional correlative studies
Correlative studies
Correlative studies
Correlative studies
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
The identification of a CY/IL-2 regimen that is considered to be safe
Time frame: Baseline, 4 weeks and 8 weeks
The identification of a CY/IL-2 regimen (among those considered safe) which yields the greatest effect on the duration of in vivo persistence of adoptively transferred CTL clones
Time frame: Baseline, 4 weeks and 8 weeks
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