A severe allergic reaction could be life- threatening. E xamples of allergic reaction s include: rash; shortness of breath; wheezing; sudden drop in blood pressure; swelling around the mouth, throat, or eyes ; fast pulse; and sweating. 7.3 Serious Adverse Events and Serious Adverse Drug Reactions The investigator must assess each event to determine if it meets the criteria for classificat ion as a serious adverse event (SAE) or serious adverse drug rea ction (ADR). An SAE/ADR i s defined in the Code of Federal Regulations (21CFR312.32) a s any event that: Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 39 of 68 J1265 PROT (Vers) 1.4 113012 • results in death • is life -threatening • results in inpatient hospitalization or prolongation of existing hospitalization • results in pers istent or significant disability or incapacity • results in congenital anomaly or birth defect • is medically significant in the opinion of the investigator All SAEs that occur any time while a patient is on study ( i.e., as soon as the informed consent has been signed) or within 30 days of the last dose of study drug administration must be d ocumented , regardless of the suspected relationship to the investigational agent (s). Any SAE occurring more than 30 days after the last dose of the study drug (s) must be recorded if a causal relationship to the investigational agent (s) is suspected. 7.3.1 Progression of m alignancy Progression of a patient’s malignancy should not be considered an AE unless , in the investigator’s opinion, study treatment resulted in an exacerbation of the patien t’s condition. If disease progression results in death or hospitalization while on study or within 30 days of the last dose of study drug administration , progressive disease will be considered an SAE. 7.3.2 Life-threatening events A life -threatening event is any AE that places the patient at immediate risk of death from the reaction as it occurs. It is not a reaction that, had it occurred in a more severe form, might have caused death. 7.3.3 Hospitalization or p rolongation of hospitalization Hospitalization encompasses a ny inpatient admission (even if < 24 hours) r esulting from a precipitating treatment -emergent adverse event. For chronic or long -term patients, inpatient admission also includes transfer within the hospital to an acute or inten sive care inpatient unit. Hospitalizations for administrative reasons or a non -worsening preexisting condition should not be considered AE s (e.g. , admission for workup of a persistent pretreatment laboratory abnormality, yearly physical exam, protoc ol-specified admission, or prostatectomy surgery). Hospitalization because of an unplanned event will be deemed an SAE. Preplanned treatments or surgical procedures should be noted in the baseline documentation. In the case of this study, all patients will have a preplanned prostatectomy surgery . Prolongation of hospitalization is any extension of an inpatient hospitalization beyond the stay anticipated or required for the original reason for admission. 7.3.4 Significant disability This i s defines as a subs tantial disruption of the patient’s ability to conduct normal life functions and activities of daily living . 7.3.5 Congenital anomaly If the female partner of a male patient becomes pregnant during the course of the study, the treating physician must be no tified immediately. All confirmed pregnancies must be immediately reported to the principal investigator and the medical monitor , and recorded in the CRF . All pregnancies will be followed until resolution ( i.e., voluntary or spontaneous termination or birt h) and as sessed for congenital anomalies and birth defects. Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 40 of 68 J1265 PROT (Vers) 1.4 113012 7.3.6 Medical significance An event that is not fatal or life -threatening and that does not necessitate hospitalization may be considered serious if, in the opinion of the investigator, it jeopardizes the patient’s status and might lead to medical or surgical intervention to prevent any of the above outcomes. Such medically significant events could include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood d yscrasias that do not result in inpatient hospitalization, or the development of drug dependency or abuse. 7.4 Perioperative Adverse Events Complications of surgery or those occurring in the early post -operative period will be recorded. These include wound complications, estimated blood loss, post -operative infections, delayed wound healing , abnormal laboratory values, etc . Duration of hospital stay will be recorded. Additional medical examinations will be allowed at the request of patients during drug admi nistration or at the discretion of the principal investigator for the evaluation of new adverse events that warrant physical examination. During and following completion of the study, patients should notify the study staff of any problems that occur betwee n visits or following study termination by telephone and, if necessary, will be evaluated by the investigator or study personnel at an unscheduled interim visit. Operative/perioperative events will be reco rded as described in Section 7.1, and their severit ies will be categorized using the NCI CTCAE version 4.0 criteria. The relationship of these events to the investigational drug (s) will be determined by the principal inv estigator together with urologist co- investigators and, if necessary, with the primary urologic surgeon . Reporting of these events will follow the same guidelines described in Section 7.5. 7.5 Reporting Adverse Events 7.5.1 Reporting serious adverse events (SAEs) All SAEs and unknown/unexpected reactions should be reported to the PI (Emmanue l Antonarakis, MD) within 24 hours. In addition, all SAEs must be reported by the PI to the IND Sponsor (Charles Drake, MD, PhD) within 24 hours. Harry Cao (phone 4 43-287-6 882, fax 410- 614-7287, hcao7@jhmi.edu ) should be contacted when reporting an SAE or death. If this person cannot b e reached within 24 hours, the PI (Emmanuel Antonarakis MD ) should be contacted at 443- 287-0553 or at eantona1@jhmi.edu . Alternatively, the co -PI (Edward Schaeffer MD, PhD) can be contacted at (410) 502- 2733 or at eschaef4 @jhmi.edu . The initial report for each SAE or death should include the following information (see also Appendix C for SAE Reporting Form) : • protocol # and title • patient initials, study identification number, sex, age • date the event occurred • description of the SAE • investigational agent received (and dose level) at the time the SAE occurred • description of the patient’s condition • indication of whether the patient remains on study Follow -up information including severity, causality, action taken, concomitant medications, and outcome should be communicate d to the principal investigator and IND Sponsor as soon as possible with an indication whether an amendment will need to be made to the protocol, the consent form , or both, as a result of this event. Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 41 of 68 J1265 PROT (Vers) 1.4 113012 7.5.2 Reporting requirements for the Sidney Kimmel Comprehensive Cancer Center (SKCCC) The principal in vestigator will notify the appropriate regulatory agencies of any SAEs occurring during the study period, regardless of causality. These agencies include the Sidney Kimmel Comprehensive Cancer Center (SKCCC) Data and Safety Monitoring Committee (DSMC), and the Institutional Review Board (IRB) and the Institutional Biosafety Committee (IBC) of the Johns Hopkins Medical Institutions (JHMI). Expedited reporting to the IND Sponsor by the PI within 24 hours is required for all SAEs (see Sectio n 7.4.1). For SAEs that are fatal, life -threatening, or treatment -related but non -life threatening : IRB/IBC reporting by the PI is required within 3 days. For unrelated SAEs, IRB/IBC reporting by the PI is required within 15 days. All other AEs should be documented on CRFs a nd submitted according to the standard data management guidelines . Adverse event information will be collected continuously throughout the duration of the study. Participants will be instructed to notify their treating provider of any new signs or symptoms , and providers will actively assess patients for adverse events at each visit (including by evaluation of laboratory studies). The investigator will assess each AE for its severity and for its relationship to the study drug, and all events Grade 1 or high er will be documented on CRFs and then reported as described above within the required time frame. Any AE occurring while a patient is on study ( i.e. after informed consent has been signed) or within 30 days of study termination requires reporting. AEs occurring later than this must still be reported if a causal relationship with the study drug is suspected. For all AEs, the investigator must pursue and obtain information to adequately determine the causality and outcome of the event, and to assess whether it meets criteria for a SAE. In addition, follow -up of an AE is required until the event either resolves or stabilizes. Initial reporting of an AE should include at a minimum the patient number, age, the dose at which the event occurred, and the type and severity of the event. Follow -up information including causality, duration, outcome, action taken, and concomitant medications should be reported soon thereafter. The principal investigator must keep copies of all CRFs and other AE information, including correspondence with the IRB and/or FDA, for as long as required to comply with national and international regulations (generally at least 3 years after study completion) . 7.5.3 FDA reporting requirements Annual IND Report All SAEs are reported to the FDA via the IND annual report per 21 CFR 312.33. SAEs deemed unexpected and related to the investigational product qualify for expedited reporting and must be submitted by the IND Sponsor -Investigator to the FDA per 21 CFR 312.32 as shown immediately below. 7 Calendar- day telephone or fax report The IND Sponsor (Charles Drake , MD, PhD ) is required to notify the FDA of any fatal or life - threatening adverse event that is unexpected and assessed by the investigator to be possibly related to the use of prostate GVAX. An unexpected adverse event is one that is not already described in this Protocol or the Consent form . Such reports are to be telephoned or faxed (301-827-9796) to the FDA within 7 calendar days o f first learning of the event. Each telephone call or fax transmission should be directed to the FDA new drug review division in the product review division for the Center for Biologics Evaluation and Research (CBER) , whichever is responsible for the review of the IND. 15 Calendar- day written report The IND Sponsor (Charles Drake , MD, PhD ) is also required to notify the FDA and all participating investigators, in a written IND Safety Report, of any serious, unexpected AE Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 42 of 68 J1265 PROT (Vers) 1.4 113012 that is considered reasonably or possibly related to the use of prostate GVAX. An une xpected adverse event is one that is not already describ ed in this Protocol or the Consent form . Written IND Safety Reports should include an “Analysis of Similar Events ” in accordance with regulation 21 CFR 312.32. All safety reports previously filed with the IND concerning simi lar events should be analyzed. The new report should contain comments on the significance of the new event in light of the previous similar reports. Written IND safety reports with “ Analysis of Similar Events ” are to be submitted to the FDA and all participating investigators within 15 calendar days o f first learning of the event. The FDA prefers these reports on the FDA 3500A Form but alternative formats are also acceptable ( e.g.