All treatment areas must have a copy of this document, or must be able to access a copy. In general, the grading system can be summarized as follows: Grade: Severity: Description: Grade 1 Mild Transient or mild discomfort; generally non -progressive; no limitation in daily activities; no medical intervention required. Grade 2 Moderate Mild/moderate limitation in daily activities; some assistance may be required; no/minimal medical intervention required. Grade 3 Severe Marked limitation in daily activities; some assistance usually required; medical intervention is required. Grade 4 Life-threatening Extreme limitation in daily activities; major assistance required; significant medical intervention required. Grade 5 Death Death related to an adverse event. Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 63 of 68 J1265 PROT (Vers) 1.4 113012 APPENDIX C: SERIOUS ADVERSE EVENT (SAE) REPORTIN G FORM Please notify Dr. Charles Drake within 24 hour s Protocol Title: A neoadjuvant immunologic study of androgen deprivation therapy combined with a GM -CSF –secreting allogeneic prostate cancer vaccine and low -dose cyclophosphamide in men with high- risk localized prostate cancer undergoing radical prostatectomy Protocol Number: J12XX Principal Investigator: Dr. Emmanuel Antonarakis Signature of PI: Date: Report Date: Hospital Admission Date: Date of Discovery of Event: Report Type: Initial Follow -up Final Follow -up Death Addendum to: Section A: Subject I nformation Subject ID: Subject Initial: Subject Gender: Male Female Section B: Event Information Event diagnosis or symptoms: Date of CY Dos e: Action taken regarding the study drugs: None Interrupted Discontinued Date of GVAX Dos e: Event Onset Date: Event End Date: Relationship to: Cyclophosphamide Prostate GVAX Underlying Disease Unrelated Probably Unrelated Possible Related Probably Related Definitely Related Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 64 of 68 J1265 PROT (Vers) 1.4 113012 Section C: Brief Description of the Event: Section D: Relevant Medical History Section E: Concomitant Drug (Not related to SAE) Name of the Drug Start Date Stop Date Route Dose Frequency Section F: Comments Additional Documents: Please specify Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 65 of 68 J1265 PROT (Vers) 1.4 113012 APPENDIX D: ABBREVIATIONS AND AC RONYMS AAV adeno -associated virus ACLS Advanced Cardiac Life Support ADR adverse drug reaction ADT androgen deprivation therapy AE adverse event ALT alanine aminotransferase ANC absolute neutrophil count ANOVA analysis of variance APTT activated partial thromboplastin time AR androgen receptor AST aspartate aminotransferase BCG bacillus Calmette -Guerin vaccine bid bis in die (twice a day) BP blood pressure BSA body surface a rea BUN blood urea nitrogen ⁰C degrees Celsius Ca++ calcium CBC complete blood count CD4+ T cells cluster determinant 4 –positive T lymphocytes CD8+ T cells cluster determinant 8 –positive T lymphocytes CFR Code of Federal Regulations CG1940 PC3-derived prostate cancer cell line expressing human GM -CSF (Cell Genesys, Inc.) CG8711 LNCaP -derived prostate cancer cell line expressing human GM -CSF (Cell Genesys, Inc.) CI confidence interval Cl− chloride cm centimeter COPD chronic obstructive pulmonary disease CR complete response CRO Clinical Research Office CRF case report form CRPC castration resistant prostate cancer CRRMC Clinical Research Review and Monitoring Committee CT computerized tomography CTL Cell Therapy Laboratory CTLA -4 cytotoxic T lymphocyte -associated antigen 4 CTCAE Common Terminology Criteria for Adverse Events CTEP Cancer Therapy Evaluation Program Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 66 of 68 J1265 PROT (Vers) 1.4 113012 DAB 3,3′-diaminobenzine tetrahydrochloride dL deciliter DLT dose -limiting toxicity DMSO dimethyl sulfoxide DNA deoxyribonucleic acid DNase deoxyribonuclease DPBS Dubelcco's phosphate buffered saline DSM C data and safety monitoring committee DTH delayed -type hypersensitivity EC ethics committee ECOG Eastern Cooperative Oncology Group EMLA eutectic mixture of local anesthetics FDA Food and Drug Administration GCP good clinical practice G-CSF granulocyte -colony stimulating factor GM-CSF granulocyte -macrophage colony -stimulating factor GnRH gonadotropin -releasing hormone GVAX allogeneic cell -based GM -CSF–secreting immunotherapy for prostate cancer HA hemagglutinin HIPAA Health Insurance Portability and Accountability Act HR heart rat e HRPC hormone -refractory prostate cancer HSA human serum albumin HSB hue-saturation -brightness IBC Institutional Biosafety Committee ICH International Conference on Harmonisation IHC Immunohistochemistry ID intradermal IND investigational new drug INR international normalized ratio IQR interquartile range IRB Institutional Review Board IV intravenous JHMI Johns Hopkins Medical Institutions K+ potassium LDH lactate dehydrogenase LHRH luteinizing hormone releasing hormone LNCaP AR-positive human prostate cancer cell line derived from a lymph node metastasis LOI letter of intent MedDRA Medical Dictionary for Regulatory Activities Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 67 of 68 J1265 PROT (Vers) 1.4 113012 MMTV murine mammary tumor virus MTD maximum tolerated dose NA not applicable N/A not available NCI National Cancer Institute OR operating room PC3 androgen -independent human prostate cancer cell line derived from a bone metastasis PI principal investigator PO per os (by mouth) PSA prostate -specific antigen PSMA prostate -specific membrane antigen PT prothrombin time PTT partial thromboplastin time qd quaque die (every day) RAC Recombinant DNA Advisory Committee RP radical prostatectomy RT room temperature SAE serious adverse event SC Subcutaneous SD standard deviation SKCCC Sidney Kimmel Comprehensive Cancer Center TdT terminal deoxynucleotidyl transferase tid ter in die (3 times a day) TMA tissue microarray TRAMP transgenic adenocarcinoma of the mouse prostate(mouse model) Tregs regulatory T lymphocytes TUNEL TdT- mediated deoxy uridine triphosphate (UTP) nick end -labeling assay ULN upper limit of normal USP United States Pharmacopeia (sterile, hypotonic, nonpyrogenic water for injection) WBC white blood cell Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 68 of 68 J1265 PROT (Vers) 1.4 113012 APPENDIX E: DATA AND SAFETY MONITORING PLAN (DSM P), Version 4.0 (9/22/11)