Study of Sipuleucel-T With or Without Continuing New Hormonal Agents in Metastatic Prostate Cancer

Inclusion Criteria:

* Asymptomatic or minimally symptomatic metastatic prostate cancer, and the diagnosis of prostate cancer needs to be histologically confirmed by biopsy of the prostate or a metastatic lesion
* On combined ADT with LHRH analog and a NHA (enzalutamide, apalutamide or abiraterone) for metastatic prostate cancer with PSA progression, but no imaging progression based on the prostate cancer working group (PCWG) 3 criteria
* Age 18 or above
* ECOG performance status 0 or 1
* Participants must have adequate organ and marrow function as defined below:
* Absolute neutrophil count ≥1,000/mcL
* Platelets ≥100,000/mcL
* Hemoglobin \> 10 g/dl
* AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
* Creatinine 1.5 ≤ institutional ULN
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of sipuleucel-T are eligible for this trial
* No uncontrolled arrhythmia: patients with h/o myocardial infarction or history of congestive heart failure, need to have estimated left ventricle ejection fraction above 40% either on echocardiogram or MUGA scan within 6 months of study enrollment
* Non-sterilized men who are sexually active with a female partner of childbearing potential must agree to use adequate contraception prior to the study enrollment, and for the duration of study participation
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
* Prior treatment with sipuleucel-T
* Participants who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2).
* Participants who require \> 50% dose reduction of NHA are excluded from the study except for taking abiraterone at 250 mg with low fat food
* Documented brain metastases or liver metastases
* Treatment with any investigational compound within 30 days prior to the first dose of Sipuleucel-T
* Documented brain metastases or liver metastases
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for sipluleucel-T to be less clinically active in this population
* Inability to comply with protocol requirements