Immediate or Delayed Ipilimumab after Sipuleucel-T Treatment in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Histologically confirmed, metastatic prostate adenocarcinoma (positive bone scan and/or measurable disease on computed tomography [CT] scan and/or magnetic resonance imaging [MRI] of the abdomen and pelvis)
• History of progressive disease after androgen deprivation, defined by one OR both of the following: * Objective radiographic progression defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria * Prostate-specific antigen (PSA) evidence for progressive prostate cancer which consists of a PSA level of at least 2 ng/ml, which has risen on at least 2 successive occasions, at least 1 week apart; if the confirmatory PSA value is not greater than the screening PSA value, then an additional test for rising PSA will be required to document progression
• If no prior orchiectomy has been performed, patients must remain on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g. degarelix) therapy; patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of the antiandrogen, defined as two consecutive rising PSA values, obtained at least two weeks apart, or documented osseous or soft tissue progression; at least one of the PSA values must be obtained at least four weeks (flutamide) or six weeks (bicalutamide or nilutamide) after discontinuation
• Absolute neutrophil count (ANC) >= 1500/uL
• Bilirubin < 1.5 x upper limit of normal (ULN)
• Hemoglobin >= 8 g/dL
• PSA >= 2 ng/mL
• Platelets >= 100,000/uL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine clearance >= 60 mL/min by the Cockcroft Gault equation
• Testosterone =< 50 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy >= 12 weeks
• Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), or any systemic corticosteroid, must discontinue the agent for at least four weeks prior to ipilimumab treatment; progressive disease as defined above must be documented after discontinuation of any hormonal therapy (with the exception of a LHRH agonist)
• Prior radiation therapy must be completed >= 2 weeks prior to enrollment and the patient must have recovered from all toxicity; prior radiopharmaceuticals (strontium, samarium, alpharadin) must be completed >= 4 weeks prior to enrollment
• Because of the unknown potential risk to a gamete and/or developing embryo from these investigational therapies, patients must agree to use adequate contraception (barrier method for males) for the duration of study participation, and for three months after discontinuing therapy

Exclusion Criteria

• Prior chemotherapy for metastatic CRPC; prior neoadjuvant chemotherapy or chemotherapy for metastatic hormone sensitive prostate cancer are allowed so long as this treatment was completed at least 6 months prior to initiation of sipuleucel-T
• Prior treatment with an anti-CTLA-4 antibody treatment; the course of sipuleucel-T therapy (i.e. three treatments) leading up to this investigational trial must be the first course of therapy these patients have received
• Prostate cancer pain requiring regularly scheduled narcotics
• Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable); systemic corticosteroids must be discontinued for at least 4 weeks prior to first treatment with ipilimumab
• History of autoimmune disease including, but not limited to: * Systemic lupus erythematosus (SLE), scleroderma, calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome, rheumatoid arthritis * Inflammatory bowel disease, celiac disease, primary biliary cirrhosis, autoimmune hepatitis * Dermatomyositis, polymyositis, giant cell arteritis * Autoimmune hemolytic anemia (AIHA), cryoglobulinemia, antiphospholipid antibody syndrome (APLS) * Diabetes mellitus type I, myasthenia gravis, Grave’s disease * Wegener’s granulomatosis or other vasculitis * A history of Hashimoto’s thyroiditis, psoriasis, or eczema, any of which has been inactive for at least one year, or isolated Raynaud’s phenomenon is acceptable
• Known central nervous system or visceral metastases
• Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
• Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
• Concurrent or prior malignancy except for the following: * Adequately treated basal or squamous cell skin cancer * Adequately treated stage I or II cancer from which the patient is currently in complete remission * Any other cancer from which the patient has been disease-free for 5 years
• Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g., infectious) illness
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea