Sipuleucel-T Manufacturing Demonstration Study

This was an open-label, uncontrolled, multi-center study. Study participants will underwent screening procedures to ensure that they met the inclusion and exclusion criteria. Subjects underwent a standard 1.5 to 2.0 blood volume leukapheresis, followed approximately 3 days later by an infusion of sipuleucel-T. This process was be repeated at approximately 2-week intervals for a total of 3 infusions.

In Austria, The Netherlands, and France, a study completion visit occurred between 30 and 37 days post-final infusion, or between 30 and 37 days post-final leukapheresis for subjects not receiving at least 1 infusion. In the UK, a follow-up visit occurred 30 days after the subject's final infusion and a study completion visit occurred 6 months after the subject's final infusion.

Inclusion criteria

• Histologically documented adenocarcinoma of the prostate
• Metastatic disease as evidenced by soft tissue and/or bony metastases on bone scan and/or computed tomography (CT) scan of the abdomen and pelvis at any time prior to registration
• Castrate resistant prostate cancer
• Serum PSA ≤ 5.0 ng/mL
• Castration levels of testosterone (≤ 50 ng/dL; ≤ 1.74 nmol/L) achieved via medical or surgical castration. Surgical castration must have occurred at least 3 months prior to registration.
• ECOG performance status ≤ 1
• Adequate hematologic, renal, and liver function
• Negative serology tests indicating no active infection with human immunodeficiency virus types 1 and 2 (HIV-1/2), human T cell lymphotropic virus types 1 and 2 (HTLV-I/II), and Hepatitis B and C viruses.

Exclusion criteria

• The presence of known brain metastases
• A requirement for systemic immunosuppressive therapy for any reason
• Treatment with any investigational vaccine within 2 years prior to registration
• Any previous treatment with sipuleucel-T
• Any previous treatment with ipilimumab (Yervoy[TM], MDX-010, or MDX-101) or denosumab (Xgeva[TM])
• Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
• Known malignancies other than prostate cancer that are likely to require treatment within 6 months of registration
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF
• More than 2 chemotherapy regimens at any time prior to registration
• Treatment with any chemotherapy within 90 days of registration
• Received granulocyte colony-stimulating factor (G-CSF) or GM-CSF within 90 days prior to registration
• Treatment with any of the following medications or interventions within 28 days of registration:
• Systemic corticosteroids. Use of inhaled, intranasal, intra-articular, and topical steroids is acceptable, as is a short course (i.e., ≤ 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans.
• Non-steroidal anti-androgens (e.g., bicalutamide, flutamide, or nilutamide)
• External beam radiation therapy or major surgery requiring general anesthetic
• Any other systemic therapy for prostate cancer including secondary hormonal therapies, such as megestrol acetate (Megace®), diethylstilbestrol (DES), and ketoconazole. Medical castration therapy is not exclusionary.
• Immunosuppressive therapy
• Treatment with any other investigational product
• Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5°F or 38.1°C) within 7 days prior to registration.
• Any medical intervention or other condition which, in the opinion of the Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.