The purpose of this study is to find out what effects, good and/or bad, taking ipilimumab with abiraterone acetate plus prednisone has on the patient and the prostate cancer. Abiraterone acetate plus prednisone are drugs that lower testosterone (testosterone stimulates prostate cancer growth). Abiraterone acetate plus prednisone is a treatment for patients with prostate cancer.

Abiraterone acetate plus prednisone has not been used together with ipilimumab before. This study will test how they work together. Each patient will receive abiraterone acetate, prednisone and ipilimumab.

Inclusion Criteria:

Chemotherapy- and immunotherapy-naïve patients with progressive metastatic CRPC are eligible.

• Age 18 or older, and be willing and able to provide informed consent.
• Histologically or cytologically confirmed adenocarcinoma of the prostate at either MSKCC or at the participating site.
• Castrate serum testosterone level, ≤ 1.73 nmol/L (50 ng/dL), at the Screening visit.
• Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy (ie, surgical or medical castration).
• Metastatic disease on imaging (e.g., bone scan, CT, MRI). Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible. If lymph node metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter.
• Progressive disease at study entry defined by PSA and/or radiographic criteria according to the PCWG2.
• Karnofsky performance status of ≥80-100, and estimated life expectancy of ≥ 6 months.
• Toxicities related to prior therapy must either have returned to ≤ Grade 1 or baseline or been deemed irreversible and in the opinion of the Investigator not worsened.
• Able to swallow the study drug and comply with study requirements.

Exclusion Criteria:

• History of another malignancy within the previous 5 years other than nonmelanomatous skin cancer.
• Absolute neutrophil count < 1,500/μL, or platelet count < 75,000/μL, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit. (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit).
• Serum bilirubin ≥ 1.5 x ULN or for patients with Gilbert's disease, ≥3 mg/dL at the Screening visit; AST or ALT ≥ 2.5 x ULN, (for patients with known liver metastasis, AST or ALT ≤ 5 x ULN is allowed) at the Screening visit.
• Creatinine > 177 μmol/L (2 mg/dL), albumin < 30 g/L (3.0 g/dL), potassium ≤ 3.5 mEq/L at the Screening visit.
• Clinically significant cardiovascular disease including myocardial infarction within 6 months, uncontrolled angina within 3 months, congestive heart failure New York Heart Association (NYHA) class 3 or 4, uncontrolled hypertension as indicated by systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg at the Screening visit.
• Major surgery or radiation therapy within 4 weeks of enrollment (Day 1 Visit).
• Treatment with antiandrogens (eg, bicalutamide, flutamide, or nilutamide) within 4 weeks of enrollment (Day 1 visit). Concomitant therapy with any of the agents listed in Section 4.3.2 is prohibited.
• History of progression of prostate cancer disease while receiving ketoconazole. Prior use or participation in a clinical trial of an investigational agent that blocks androgen synthesis (eg, abiraterone acetate, TAK-700, TAK-683, TAK-448), chemotherapy, or immunological agents (eg, immune modulators, cytokines, vaccines, or antibody-delivered chemotherapy). The use of denosumab for bone metastasis is permitted.
• Known allergy to any of the compounds under investigation.
• The patient has uncontrolled or significant medical condition other than cancer, that would prevent the participation in the study or make this protocol unreasonably hazardous, in the opinion of the investigator, including but not limited to:
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (eg, Guillain-Barre syndrome and myasthenia gravis).
• Known or suspected brain metastasis, or untreated leptomeningeal disease.
• Active infection or other medical condition that would make prednisone use contraindicated.
• Active or symptomatic viral hepatitis or chronic liver disease.