Therapeutic Autologous Lymphocytes, Aldesleukin, and Denileukin Diftitox in Treating Patients With Stage IV Melanoma

PRIMARY OBJECTIVES:

I. Assess the safety of cellular adoptive immunotherapy in melanoma patients using
autologous CD8+ antigen-specific T-cell clones following CD25 lymphodepletion.

II. Determine the influence of CD25 lymphodepletion on the duration of in vivo persistence
of adoptively transferred CD8+ antigen-specific CTL clones.

SECONDARY OBJECTIVES:

I. Assess the anti-tumor efficacy ofcellular adoptive immunotherapy in melanoma patients
using autologous CD8+ antigen-specific T cell clones following CD25 lymphodepletion.

II. Evaluate the induction of T cells to non-targeted tumor-associated antigens
(antigen-spreading) following adoptive transfer of CD8+ antigen-specific CTL and CD25
lymphodepletion.

OUTLINE:

This is a phase I study followed by a phase II study.

Patients receive autologous T-cell infusion over 30-60 minutes on days 0 and 28 and low-dose
aldesleukin (IL-2) subcutaneously (SC) twice daily on days 0 to 13 and 28 to 41. Beginning
4-6 days before second T- cell infusion, patients receive denileukin difitox IV over 30
minutes on days 1-3. 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 then
every 3 months thereafter.