Inclusion Criteria:

- Patients must have unresectable stage III or stage IV melanoma, either initial
presentation or recurrent, that is of cutaneous origin or unknown primary origin,
that is histologically diagnosed

- No more than one prior systemic therapeutic regimen for unresectable stage III or
stage IV melanoma; this includes chemotherapy, biologic therapy, biochemotherapy, or
investigational treatment; this does not include any therapies given in the adjuvant
setting; however, patients are excluded if they have a history of prior treatment for
melanoma (either adjuvant or metastatic disease) with ipilimumab or other cytotoxic
T-lymphocyte antigen 4 (CTLA-4) inhibitor, or prior interferon-alpha treatment for
metastatic disease (history of adjuvant interferon-alpha is allowed)

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of
0-1

- Patients must not have other significant medical, surgical, or psychiatric conditions
or require any medication or treatment that in the opinion of the investigator may
interfere with compliance, make the administration of Ipilimumab or HDI hazardous or
obscure the interpretation of adverse events (AEs), such as a condition associated
with frequent diarrhea; patients must not have an active infection requiring current
treatment with parenteral antibiotics

- Patients must not have a history of inflammatory bowel disease or diverticulitis
(history of diverticulosis is allowed)

- Patients who have other current malignancies are not eligible; patients with other
malignancies are eligible if they have been continuously disease free for > 5 years
prior to the time of randomization; one exception are patients treated with a
curative intent and are continuously disease free for > 3 years; these patients would
be considered eligible:

- Patients with prior history at any time of any in situ cancer, lobular carcinoma
of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia
or Clark I melanoma in situ are eligible

- Patients with prior history of basal or squamous skin cancer are eligible

- Patients must not have autoimmune disorders or conditions of immunosuppression that
require current ongoing treatment with systemic corticosteroids (or other systemic
immunosuppressants), including oral steroids (e.g., prednisone, dexamethasone) or
continuous use of topical steroid creams or ointments or ophthalmologic steroids; a
history of occasional (but not continuous) use of steroid inhalers is allowed;
replacement doses of steroids for patients with adrenal insufficiency are allowed;
patients who discontinue use of these classes of medication for at least 2 weeks
prior to randomization are eligible if, in the judgment of the treating physician
investigator, the patient is not likely to require resumption of treatment with these
classes of drugs during the study; exclusion from this study also includes patients
with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis,
systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's
syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy
considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia
Gravis); other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis,
multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes
on replacement treatment are eligible

- Due to the possible effect of treatment with ipilimumab on the immunologic response
to infectious disease vaccines, patients must not have had any infectious disease
vaccination (e.g, standard influenza, H1N1 influenza, pneumococcal, meningococcal,
tetanus toxoid) within 4 weeks prior to randomization

- Women must not be pregnant or breast-feeding due to the unknown effects of ipilimumab
and the combination with HDI on conception and the fetus; all females of childbearing
potential must have a blood test or urine study during screening to rule out
pregnancy; NOTE: A woman of childbearing potential (WOCBP) is any woman, regardless
of sexual orientation or whether they have undergone tubal ligation, who meets the
following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or 2)
has not been naturally postmenopausal for at least 24 consecutive months (i.e., has
had menses at any time in the preceding 24 consecutive months); for the purposes of
this study, post-menopause is defined as:

- Amenorrhea >= 24 consecutive months without another cause, or

- For women with irregular menstrual periods and taking hormone replacement
therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35
mIU/mL Women who are using oral contraceptives, other hormonal contraceptives
(vaginal products, skin patches, or implanted or injectable products), or
mechanical products such as an intrauterine device or barrier methods
(diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing
abstinence or where their partner is sterile (e.g., vasectomy) should be
considered to be of childbearing potential; men of fathering potential and WOCBP
must be using an adequate method of contraception or must abstain from sexual
intercourse to avoid conception/pregnancy throughout the study and for up to 26
weeks after the last dose of ipilimumab or HDI in such a manner that the risk of
pregnancy is minimized; men or WOCBP who are unwilling or unable to strictly
follow this requirement are not eligible

- White blood cells (WBC) >= 3000/uL

- Absolute neutrophil count (ANC) >= 1500/uL

- Platelets >= 100 x 10^3/uL

- Hemoglobin >= 10 g/dL

- Serum creatinine =< 1.8 mg/dl

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN) for patients with liver metastases and =< 2.0 x ULN for patients
without liver metastases

- Serum bilirubin < 2 x ULN for patients with liver metastases and =< 1.5 x ULN for
patients without liver metastases, (except patients with Gilbert's syndrome, who must
have a total bilirubin < 3.0 mg/dL)

- No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B,
or hepatitis C due to the unknown effects of ipilimumab or the combination with HDI

- Patients must be free of brain metastasis by contrast-enhanced computed tomography
(CT)/magnetic resonance imaging (MRI) scans within 4 weeks prior to enrollment; if
known to have prior brain metastases, must not have evidence of active brain disease
after definitive therapy (surgery, radiation therapy or stereotactic radiosurgery) on
two successive MRI evaluations at least 3 months apart (one of which is =< 4 weeks
prior to starting the study drugs)

- All sites of disease must be evaluated within 4 weeks prior to randomization;
patients must have measurable disease as defined by Response Evaluation Criteria in
Solid Tumors (RECIST) v1.1