Inclusion Criteria:

- Patients must have a written informed consent obtained prior to the initiation of
study procedures.

- Male and female subjects greater than or equal to 18 years of age.

- Patients must have histologically confirmed recurrent stage III or stage IV melanoma
(AJCC 6th edition classification). Cutaneous melanoma, ocular or mucosal melanoma
will be eligible.

- Patients must have measurable disease as defined by the Response Evaluation Criteria
in Solid Tumors (RECIST). Baseline measurements must be obtained within 4 weeks prior
to initiating therapy.

- Patients must have adequate hematologic, renal, and liver function as evidenced by
the following (within 4 weeks prior to starting the study drugs):

- WBC greater than or equal to 3,000/mm3

- Lymphocytes greater than or equal to 1,000/mm3

- Platelets greater than or equal to 100,000/mm3

- Serum Creatinine less than or equal to 1.5 x upper limit of normal (ULN)

- Serum Bilirubin less than or equal to 1.5 x ULN

- Serum AST/ALT less than or equal to 2.5 x ULN

- Serum LDH less than or equal to 2.0 x ULN

- APTT less than < 40 s

- Patients must have fully recovered from any effects of major surgery, and be free of
significant detectable infection.

- Patients must not have received any chemotherapy, hormonal therapy, radiotherapy, or
biological therapy within the preceding 4 weeks.

- Patients must not have previous therapy with Anti-CTLA4 monoclonal antibodies
(including CP-675,206 and MDX-010). Previous therapy with Interferon-alfa 2b in the
adjuvant or metastatic setting is allowed. Previous therapy with other biological
agents (including vaccines and GM-CSF) is allowed.

- Patients must have ECOG performance status of 0 or 1.

- Patients must not have autoimmune disorders (except vitiligo). Patients with positive
titers for autoimmune antibodies are allowed on the study in the absence of history
of clinical manifestations of autoimmune disease.

- Patients must not have conditions of immunosuppression or chronic requirement for
treatment with systemic steroids, including oral steroids, continuous use of topical
steroid creams or ointments, or any inhaled steroid containing inhalers. Patients who
discontinue use of these classes of medication for at least 2 weeks are eligible.
Treatment with steroids or other immunosuppressant medications is allowed during the
study if clinically required to treat side effects related to autoimmunity that may
develop secondary to the study agents.

- Patients must be free of brain metastasis by contrast-enhanced CT/MRI scans within 4
weeks prior to starting the study drugs. If known to have prior brain metastases,
must not have evidence of active brain disease on two successive MRI evaluations at
least 3 months apart (one of which is £ 4 weeks prior to starting the study drugs).

- Female patients of child bearing potential must have a negative pregnancy test, and
must not be breast feeding.

- Patients must agree to use effective contraception (both males and females).

Exclusion Criteria

- Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart
failure, hypertension, cardiac ischemia, myocardial infarction, severe cardiac
arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or
restrictive pulmonary diseases, active systemic infections, and inflammatory bowel
disorders.

- Treatment with mitomycin C or nitrosureas within six weeks prior to study entry.

- Any significant psychiatric disease, medical intervention, or other condition, which
in the opinion of the principal investigator, could prevent adequate informed consent
or compromise participation in the clinical trial.

- Active infection or antibiotics within one-week prior to study, including unexplained
fever (temp > 38.1°C).

- Treatment with anticoagulants, except to keep an indwelling line patent.

- Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the
study.

- Treatment with any investigational product within 28 days of registration.

- History of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis),
celiac disease, or other chronic gastrointestinal conditions associated with
diarrhea, or current acute colitis of any origin, or any history of diverticulitis
(even a single episode) or evidence of diverticulitis at baseline, including evidence
limited to CT-scan only.

- Patients who did not tolerate high-dose interferon-α therapy in the adjuvant setting
will be excluded.