Phase II Trial of ONTAK With Metastatic Melanoma

Inclusion Criteria

Only patients with distant metastases from cutaneous or mucosal melanoma or melanoma of
unknown primary are eligible for this study.

- Only patients with distant metastases from cutaneous or mucosal melanoma or melanoma
of unknown primary are eligible for this study. All patients must fulfill the
following criteria:

- Primary tumor must be documented by histopathologic analysis

- Measurable disease defined as at least one lesion that can be accurately and
serially measured per the modified RECIST criteria (Appendix). Cutaneous lesions
measuring at least 1 cm will be considered measurable. Measurements must be
documented by radiologic examinations (CT scan, PET scan).

- Disease recurrences occurring greater than five years after the original
diagnosis must be biopsy proven.

- Patients with lymph node metastases in multiple lymph node beds who are not
amenable to surgical resection will be included in this study. Those patients
with involvement of a single lymph node bed are not eligible.

- Liver Function: Patients must have adequate hepatic function documented by a serum
bilirubin < 1.5 x the institutional upper limit of normal and liver enzymes (SGOT or
SGPT and LDH and alkaline phosphatase) <2X the institutional upper limit of normal
within 28 days prior to registration.

- Bone Marrow Function: Patients must have an absolute granulocyte count > 1,500/ul and
platelet count > 100,000/ul obtained within 14 days prior to registration.

- Renal Function: Patients must have either a serum creatinine <1.5 mg/dl or a
calculated creatinine clearance > 75 cc/min using the following formula:

- Estimated Creatinine Clearance = (140-age) X WT(kg) X 0.85 (if female 0.72) X
creatinine (mg/dl) These tests must have been performed within 28 days prior to
registration.

- Patients must have a MRI of the head performed within four weeks prior to
registration.

- Cardiac Function: Patients must not have a history of ventricular fibrillation, sinus
node or AV nodal disease, Wolff Parkinson White Syndrome, evidence of congestive
heart failure, symptoms of coronary artery disease, serious cardiac arrhythmia, or
evidence of prior myocardial infarction on EKG. The qualifying EKG must have been
performed prior to study registration, but no earlier than 28 days prior to the
definitive surgery. A normal cardiac stress test within 182 days prior to
randomization is required for all patients over 50 years old or those with abnormal
EKG or any history of cardiac disease.

- Patients must not have evidence of symptomatic pulmonary disease. PFT's within 182
days prior to registration showing a FEV1 > 2.0 liters or >75% of predicted are
required for patients over 50 or with history of pulmonary symptoms.

- Patients with known autoimmune disorders, conditions of immunosuppression or
treatment with systemic corticosteroids are not eligible for this study. Patients
with known AIDS or HIV-1 associated complex or known to be HIV antibody seropositive
are not eligible for this study.

- All patients must be 18 years of age or older.

- All patients must have a Zubrod Performance Status of 0 -1

- Patients must not be planning to receive concomitant other biologic therapy,
radiation therapy, hormonal therapy, other chemotherapy, surgery, or other therapy
while on this protocol.

- Pregnant or nursing women may not participate in this trial. Women/men of
reproductive potential may not participate unless they have agreed to use an
effective contraceptive method. A beta HCG pregnancy test is required within 14 days
of registration for women of childbearing potential.

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease-free for 5 years.