Inclusion Criteria:

- Men and women, at least 18 years of age

- ECOG performance status 0 or 1

- Histologic diagnosis of melanoma staged:

- Tx or T1-4 and

- N1b, or N2b, or N2c, or N3

- M 0 that may present as any of the following groups:

- Primary melanoma with clinically apparent regional lymph node metastases, biopsy
confirmed

- Clinically detected recurrence of melanoma at the proximal regional lymph node(s)
basin, biopsy confirmed

- Clinically or histologically detected primary melanoma involving multiple regional
nodal groups, biopsy confirmed

- Clinically detected single site of nodal metastatic melanoma arising from an unknown
primary, biopsy confirmed

- Patients with intransit or satellite metastases with or without lymph node
involvement are allowed if considered surgically resectable at baseline by the
treating medical oncologist and surgical oncologist.

NOTE: All patients must be determined to be surgically resectable at baseline to be
eligible for this neoadjuvant study.

- Patients must undergo biopsy (punch) or open biopsy (if done as part of a clinically
indicated baseline diagnostic procedure) within 14 days of entry into the study.
Lymphadenectomy/definitive surgery will be performed after at least 2 and generally
not longer than 4 weeks of induction HDI-ipilimumab therapy. Additional delays for
definitive lymphadenectomy/surgery are allowed if clinically indicated while awaiting
the resolution of potential adverse events from HDI-ipilimumab therapy.

- Patients must have been evaluated by standard-of-care full body imaging studies (CT,
PET-CT or MRI) as part of the initial clinical work-up at baseline (no more than 4
weeks prior to study enrollment) and after completion of induction HDI-ipilimumab (at
6-8 weeks after the first dose of ipilimumab/HDI and prior to the definitive
lymphadenectomy procedure).

- Required values for initial laboratory tests:

- WBC ≥ 3000/uL

- ANC ≥ 1500/uL

- Platelets ≥ 100 x 103/uL

- Hemoglobin ≥ 10 g/dL

- Creatinine ≤ 1.8 mg/dL

- AST/ALT ≤ 2.5 x ULN

- Bilirubin ≤ 1.5 ULN, (except patients with Gilbert's Syndrome, who must have a
total bilirubin less than 3.0 mg/dL)

- No active or chronic infection with HIV, Hepatitis B, or Hepatitis C

Exclusion Criteria:

- Clinical, radiological/laboratory, or pathological evidence of distant metastatic
disease.

- Evidence of soft tissue involvement by gross extranodal extension of tumor manifest
by fixation to the fascia, or matting of nodal tissue that would compromise surgical
resection as determined by the surgical oncologist.

- History of acute diverticulitis, intra-abdominal abscess, GI obstruction and
abdominal carcinomatosis which are known risk factors for bowel perforation.

- Any other malignancy from which the patient has been disease-free for less than 5
years, with the exception of adequately treated and cured basal or squamous cell skin
cancer, superficial bladder cancer or carcinoma in situ of the cervix.

- Autoimmune disease exclusions: a history of inflammatory bowel disease, a history of
symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis
[scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's
Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.
Guillain-Barre Syndrome).

- Any underlying medical or psychiatric condition, which in the opinion of the
Investigator/Sub-Investigator will make the administration of ipilimumab or HDI
hazardous or obscure the interpretation of AEs, such as a condition associated with
frequent diarrhea.

- Underlying heart conditions if deemed ineligible for surgery by cardiology consult.

- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
to 1 month before or after any dose of ipilimumab).

- Prior treatment with ipilimumab or CD137 agonist or CTLA-4 inhibitor or agonist.

- Prior radiotherapy, chemotherapy, including infusion or perfusion therapy for current
disease or any immunotherapy including tumor vaccines, interferon-alfa, interleukins,
levamisole or other biologic response modifiers within the past 4 weeks.

- Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy
regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation
therapies; or chronic use of systemic corticosteroids; unless discontinued ≥ 4 weeks.
A history of occasional use of steroid inhalers is allowed.

- Women of childbearing potential (who:

- Are unwilling or unable to use an acceptable method of contraception to avoid
pregnancy for their entire study period and for at least 26 weeks after cessation of
study drug, or

- Have a positive pregnancy test at baseline, or

- Are pregnant or breastfeeding.