10 1.1 Primary Objectives ................................................................................................................................................... 10 1.2 Secondary Objectives ............................................................................................................................................... 10 2. BACKGROUND AND RATION ALE ...................................................................................................................... 10 2.1 Disease Background ................................................................................................................................................. 10 2.2 Treatment Background ........................................................................................................................................... 11 2.3 Rationale ...................................................................................................................................................................... 17 3. PATIENT SELECTION ........................................................................................................................................... 20 3.1 Target Population ...................................................................................................................................................... 20 3.2 Inclusion Criteria ....................................................................................................................................................... 20 3.3 Exclusion Criteria ...................................................................................................................................................... 20 3.4 Inclusion of Minorities ............................................................................................................................................. 21 3.5 Prohibited Concomitant Medications ................................................................................................................. 21 4. REGISTRATION AND ENR OLLMENT PLAN .................................................................................................... 22 4.1 Registration Procedure ........................................................................................................................................... 22 4.2 Expected Enrollment ................................................................................................................................................ 22 4.3 Study Centers .............................................................................................................................................................. 22 4.4 Recruitment ................................................................................................................................................................ 23 4.5 Randomization ........................................................................................................................................................... 23 5. STUDY PLAN .......................................................................................................................................................... 23 5.1 Overview and Schema .............................................................................................................................................. 23 5.2 Screening/Pretreatment Evaluation ................................................................................................................... 26 5.3 Radical Prostatectomy ............................................................................................................................................. 26 5.4 Sera for Immunoassays ........................................................................................................................................... 27 5.5 Follow -Up Evaluation .............................................................................................................................................. 27 5.6 Duration of Therapy ................................................................................................................................................. 27 6. THERAPEUTIC AGENTS ...................................................................................................................................... 28 6.1 Prostate GVAX Immunotherapy ........................................................................................................................... 28 6.2 Low -Dose Cyclophosphamide ............................................................................................................................... 32 6.3 Degarelix Acetate ....................................................................................................................................................... 33 6.4 Concomitant Medications and Supportive Care .............................................................................................. 35 6.5 Drug Interactions/Cautions ................................................................................................................................... 36 6.6 Drug Dispensing Log ................................................................................................................................................ 36 6.7 Pregnancy .................................................................................................................................................................... 36 7. ADVERSE EVENTS AND R EPORTING REQUIREMENT S ............................................................................... 36 7.1 Recording and Grading ............................................................................................................................................ 37 7.2 Unexpected Adverse Events .................................................................................................................................. 38 7.3 Serious Adverse Events and Serious Adverse Drug Reactions .................................................................. 38 7.4 Perioperative Adverse Events ............................................................................................................................... 40 7.5 Reporting Adverse Events ...................................................................................................................................... 40 7.6 Pregnancy .................................................................................................................................................................... 42 8. OUTCOME ASSESSMENT ..................................................................................................................................... 42 8.1 Radical Prostatectomy Specimen ......................................................................................................................... 42 8.2 Primary Endpoints .................................................................................................................................................... 43 8.3 Secondary Endpoints ............................................................................................................................................... 44 9. REGULATORY AND REPORT ING REQUIREMENTS ...................................................................................... 46 9.1 Regulatory Responsibilities ................................................................................................................................... 46 Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 9 of 68 J1265 PROT (Vers) 1.4 113012 9.2 Data Management ..................................................................................................................................................... 47 9.3 Study Monitoring and Quality Assurance .........................................................................................................