Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma

Exclusion Criteria

• •Participants will not be entered in the study for any of the following:
• •1. Known central nervous system (CNS) lesions, except for asymptomatic non-progressing, treated brain metastases.
• •Treated brain metastases are defined as having no evidence of progression or hemorrhage for 2 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computerized tomography \[CT\]) during the Screening period (using the pretreatment brain image as Baseline). Treatment for brain metastases must have been completed at least 2 months prior to Day 1 of the first treatment cycle and may include whole brain radiotherapy, radiosurgery (Gamma Knife, LINAC, or equivalent), or a combination as deemed appropriate by the treating physician. Dexamethasone must be discontinued at least 4 weeks prior to Day 1. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 2 months prior to Day 1 will be excluded;
• •2. Carcinomatous meningitis;
• •3. Prior treatment with denileukin diftitox;
• •4. Known hypersensitivity to denileukin diftitox or any of its components: diphtheria toxin, IL-2, or excipients;
• •5. Prior surgery for melanoma less than 4 weeks before enrollment;
• •6. Other malignancy within 3 years of randomization, with the exception of adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer, with no subsequent evidence of recurrence and/or malignancies diagnosed at a stage where definitive therapy results in near certain cures. The Medical Monitor must be consulted in such cases;
• •7. Currently receiving any other anticancer treatment for melanoma (including palliative radiotherapy);
• •8. Received treatment in another clinical study within the 4 weeks prior to commencing study treatment or participants who have not recovered from side effects of an investigational drug to Common Terminology Criteria for Adverse Events (CTCAE) Grade less than or equal to 1, except for alopecia;
• •9. Received radiotherapy for non-CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation-related toxicities to Grade less than or equal to 1, except for alopecia;
• •10. Significant cardiovascular impairment (history of congestive heart failure New York Heart Association \[NYHA\] Grade greater than 2 \[see Appendix 5\], unstable angina, or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
• •11. Use of chronic systemic steroids (\>5 days) within 2 weeks of Day 1 of the first treatment cycle (replacement therapy for adrenal insufficiency is allowed);
• •12. Participants with an allograft requiring immunosuppression;
• •13. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive;
• •14. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures; Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study.