The goal of this clinical research study is to study the impact of ipilimumab on the immune system of patients currently receiving hormone therapy. The safety of these drug combinations will also be studied.

This is an investigational study. Ipilimumab is FDA approved and commercially available for the treatment of melanoma. Its use to treat prostate cancer is investigational.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive ipilimumab by vein over about 90 minutes at Weeks 1, 4, 7, and 10. Your blood pressure will be measured every 30 minutes during the infusion, as well as an hour after you are finished receiving the study drug.

You will continue to receive your current hormone therapy as scheduled.

You will be given standard drugs (such as steroids) to help decrease severe side effects. You may ask the study staff for information about how the drugs are given and their risks.

Study Visits:

You will have a study visit before each dose of ipilimumab, then every 4 weeks for a total of 3 visits after the last dose of ipilimumab. At each of these visits, the following tests and procedures will be performed:

• You will have a physical exam.
• Blood (about 3 tablespoons) and urine will be collected for routine tests. This blood will also be used and to measure your protein, PSA levels.
• Blood (up to 7 tablespoons) and urine will be collected to test for biomarkers. (Weeks 7, 14, and 22 only)
• Blood (about 1½ teaspoons) will be drawn to check your testosterone level. (Week 10 only)
• Blood (up to 10 tablespoons) will be drawn to test your immune system. You will sign a separate consent form for this blood draw.

At Weeks 14 and 22, the following tests and procedures will be performed to check the status of the disease:

• You may have a chest x-ray.
• You will have CT scans or MRIs of the abdomen, pelvis. If the doctor thinks it is needed, you will also have a CT scan of the chest. If a CT scan of the chest is done, a chest x-ray is not required.
• You will have a bone scan.

If the study doctor thinks it is needed, you may have additional bone scans or CT scans or MRIs of the abdomen, pelvis, or chest to check the status of the disease.

Length of Study:

You may receive the study drug for up to 10 weeks. You will remain on study (receiving your standard hormone therapy) for up to a total of 22 weeks. You will be taken off study treatment if you have intolerable side effects, if the disease gets worse, or if you are unable to follow study directions. If you develop certain side effects or have certain side effects for a long period of time, you may be taken off study. The study doctor will let you know if you need to be taken off study.

Inclusion Criteria:

1. Signed written Informed Consent for this protocol.
2. Agreed to participate in laboratory protocol PA13-0291 for the testing of biomarkers as described in this clinical protocol.
3. Patients included in the study must be >/= 18 years old.
4. Histologically or cytologically confirmed carcinoma of the prostate.
5. Subjects must have metastatic prostate cancer mass tissue collection within 3 months of study entry.
6. Evidence of metastatic disease on previous bone scan, CT scan and/or MRI.
7. Asymptomatic or minimally symptomatic.
8. Tumor progression while on hormone therapy with castrate levels serum testosterone (</= 1.7 nmol/L or 50 ng/dL) defined as biopsy-proven, PSA and/or radiographic criteria according to the Prostate Cancer Working Group 2 (PCWG2).Castrate levels of testosterone must be maintained by surgical or medical means throughout the conduct of the study.
9. ECOG performance status </= 1.
10. Patients must have normal organ and marrow function as defined below: a) WBC >/= 2500/uL.; b) ANC >/= 1000/uL.; c) Platelets >/= 75 x 10^3/uL.; d) Hemoglobin >/= 9 g/dL.; e) Creatinine \