Any adverse events should be documented and recorded on the appropriate Case Report Form. Human Serum Albumin (HSA) The prostate GVAX v accine is formulated in a cryoprotectant containing 2% human serum albumin. Albumin solutions are FDA -approved for volume resuscitation (treatment of hypovolemia, shock, and burns). Although hypersensitivity reactions are possible, reactions are not antici pated to the small amount of albumin administered in this study . Hetastarch (6%) The prostate GVAX v accine is formulated in a cryoprotectant containing 6% hetastarch in 0.9% sodium chloride. Toxicities associated with the intravenous administration of 6% hetastarch include circulatory overload , abnormalities of coagulation (prolonged prothrombin, activated partial thromboplastin and clotting times), and hypersensitivity reactions characterized by wheezing, urticaria, hypotension, and anaphylactic/ anaphyla ctoid reactions. 6.1.2.2 Potential Toxicities of the Johns Hopkins Prostate GVAX I mmunotherapy The Johns Hopkins prostate GVAX immunotherapy will consist of two a llogeneic prostate cell lines (PC3 and LNCaP). GM -CSF–secreting vaccines have been administered to over 300 patients at Johns Hopkins and toxicities have been limited to localized vaccine site reactions inv olving erythema and tenderness. Rarely, systemic reactions have been reported such as low -grade fevers and Grover’s syndrome ( transient acantholytic d ermatosis ). The GM -CSF released by the PC3/LNCaP cells after injection may also cause side effects. Redness at old injection sites may retu rn long after the administration of GVAX . The following side effects have also been reported by people taking GM -CSF: fever, chills, weakness, headache, bone pain, and muscle aches. Other side effects reported less often are difficulty b reathing, rash, fluid overload/anasarca , tachycardia, arrhythmia, leukopenia , pain ( e.g. abdomen , back, chest, and joint pain ), venous thrombosis , abnormal liver function tests, and pleural/pericardial effusions . GVAX contains porcine trypsin , fetal bovine serum , dextran sulfate and DNase and could cause an allergic reaction in sensitized individuals. There is a possible risk of a severe allergic reaction (anaphylaxis) to GVAX . The LNCaP cell line contains very small amounts of fetal bovine serum. There is a remote possibility that bovine serum may contain known or unknown infectious agents that may cause human disease, such as Creutzfeld t-Jakob (mad cow) disease. There is a sligh t possibility that GVAX could cause autoimmune disease . This has only been observed when GVAX was combined with the CTLA4- blocking monoclonal antibody , ipilimumab . There is a theoretical concern that people who receive gene therapy may develop a new cancer. Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 31 of 68 J1265 PROT (Vers) 1.4 113012 A single dose of GVAX given 2 weeks prior to prostatectomy is not expected to cause side -effects t hat would potentially delay surgery or negatively affect surgical outcomes . Nonetheless, its influence on prostat ectomy will be closely m onitored. GVAX is an experimental product that may have other side effects that are unknown and have not been predicted. These side effects may be serious. 6.1.2.3 Potential Toxicities Observed with the Cell Genesys Prostate GVAX® Cell Genesys Prostate GVAX® has been given to at least 1200 men with hormone- refractory prostate cancer in prior clinical studies. Nearly all men developed swelling and redness where CG1940 (PC3) and CG8711 (LNCaP) were injected. Most of the men also had itching and pain at the injection site. In addition, other reported side effects were fatigue, malaise, headache, myalgias, arthralgias, fever, chills/rigors, rash, anemia, weight loss, nausea, decreased appetite, flu -like symptoms, weakness, constipation, general body pains, dizziness, back pain, and hives. In a trial comparing Cell Genesys GVAX ® to docetaxel, an increase in serious urinary tract obstructions was noticed in patients that received GVAX® as compared to those that received docetaxel. In that study, three patients had serious side effects that may have been related to GVAX ®, and later died. An 82 year -old man died in his sleep four days after his first GVAX® treatment; the cause of his death was unknown. After a fall, another man had a subdural hematoma, thrombocytopenia, and later died. A third man had a stroke which resulted in death. In another trial comparing docetaxel/ GVAX® to docetaxel/prednisone, adverse events on the vaccine arm included infections, anemia, metabolic disturbances, altered mental status, abnormal coordination, seizure, cardiovascular complications, respiratory complications, abnormal taste, abdominal pain, chest pain, cough, hypertension, flushing , gastrointestinal disturbance, musculoskeletal effects, renal impairment, and fractures. It is unclear whether or not these side effects were related to GVAX®, docetaxel, or due to the omission of prednisone in that treatment arm. In addition, there were 8 deaths in the GVAX® arm in that trial that were not attributable to prostate cancer progression. These deaths were caused by cardiac arrest (2), respiratory arrest (1), myocardial infarction (1), intracranial bleed (1), ischemic encephalopathy (1), pneumonia (1), and failure to thrive (1). Additional serious side effects have been reported as being related to GVAX ® when given alone: anemia, deep venous thrombosis, sensorineural hearing loss, difficulty walking, weakness in the lower legs, severe joint pain, severe muscle pain, worsening of existing arrhythmia, dehydration resulting in kidney failure, hypercalcemia, nausea, vomiting, weight loss, pulmonary embolism, shortness of breath, fever, diarrhea, and malaise. Also, GVAX ® may possibly be related to hypothyroidism and adrenal insufficiency. 6.1.3 Treatment Modifications and Dos ing Delays Since only a single dose of prostate GVAX will be administered to each patient (arm B only) , dose modifications or treatment delays will not be permitted. 6.1.4 Supportive Care and Concomitant Medications Injection site reactions: EMLA cream (or a similar product) should be applied to the site of vaccination at a dose of approximately 2.5 grams per site approximately one hour prior to vaccination to mitigate injection -site pain. Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 32 of 68 J1265 PROT (Vers) 1.4 113012 Nau sea/ vomiting: GVAX does not typically induce nausea or vomiting. However, prochlorperazine may be given for this indication at a dose of 10 mg by mouth or intravenously as frequently as every 6 hours . Oral or intravenous corticosteroid use is not permitted . However, prophylactic antiemetic therapy at the discretion of the treating physician is allowed . During treatment (and for at least 60 minutes afterwards) , patients should be observed for adverse reactions. Treatment areas should have ACLS -certified perso nnel on site, as well as access to appropriate supportive car e modalities including but not limited to oxygen administration, corticosteroids, antihistamines and catecholamines. Any or all of these modalities may be used in the case of hypersensitivity rea ctions or anaphylactic reactions. The interaction of PC3 /LNCaP and other vaccines has not been studied, and t here is a possibility that PC3 /LNCaP may affect the immune response to oth er vaccines and vice versa . Whenever possible, patients should not receive another vaccine within 30 days of a dose of GVAX . However, medically indicated vaccines should not be delayed if doing so may be detrimental to the patient. 6.2 Low -Dose Cyclophosphamide 6.2.1 Dosage and Schedule Immunomodulatory cyclophosphamide will b e given in the outpatient setti ng as a single administration, about 4 weeks prior to prostatectomy. It will be given at a dose of 20 0 mg/m2, one day before administrat ion of prostate GVAX . It will only be given to patients in arm B . 6.2.2 Formulation and Preparation Cyclophosphamide is a sterile, white, lyophilized powder containing 75 mg mannitol per 100 mg c yclophosphamide (anhydrous) supplied in 100 mg, 200 mg, 500 mg, 1000 m g, and 2 000 mg vials for single -dose intravenous administration . Lyophilized cyclophosphamide should be prepared for parenteral (intravenous) use by adding sterile water for i njection (USP) to the vial, and shaking to dissolve. Vials containing 100 mg, 200 mg, 500 mg, 1000 m g, and 2 000 m g should be reconstituted with 5 ml, 10 ml, 20 ml, 50 ml, and 100 ml respectively. Cyclophosphamide may be infused intravenously using the following solutions: 5% dextrose, 5% d extros e and 0.9% sodium chloride, 5% dextrose and Ringer’s injection USP, lactated Ringer’s injection USP, or sodium lactate injection USP. Vials of cyclophosphamide are stable at room temperature and at temperatures less than 32°C . Reconstituted parenteral solutions are stable for 24 hours at room temperature (RT) , or for 14 days if refrigerated at 2 -8°C. After 24 hours at RT, or 14 days at 2-8°C , reconstituted cyclophosphamide must be discarded . 6.2.3 Drug Administration Cyclophosphamide will be obtained from a commercial supplier and prepared as per the institutional standard procedures . Cyclopho sphamide will be administered by intravenous infusion over 30 min in the outpatient setting. Cyclophosphamide should not be mi xed or diluted with other drugs . 6.2.4 Potential Toxicities Toxicity will be assessed using the most recent National Cancer Institute Common Toxicity Criteria for Adv erse Events (NCI CTCAE version 4 .0 – see Appendix B). Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 33 of 68 J1265 PROT (Vers) 1.4 113012 The dose of cyclophos phamide proposed in this trial is below those common ly used when this agent is employed as a cytotoxic drug ( e.g. typically 600 mg/m2 of cyclophosphamide is used per treatment cycle in breast cancer chemotherapy) . In addition, a 200 mg/m2 dose of cyclophosphamide is at about 1/ 9th the dose used for pre -conditioning during bone marrow transplant or for primary management of some autoimmune disorders. Therefore, we anticipate t hat the risk of toxicity related to the use of a single dose of cyclophosphamide at 200 mg/m2 is very smal l. Based on the toxicity evaluations of higher dose of cyclophosphamide (600 mg/m2), the most common adverse events with this agent include fatigue, a lopecia, nausea, vomiting, diarrhea, fluid retention, skin rash, cytopenias , and infections . In ad dition, hemorrhagic cystitis, interstitial pneumonitis, and cardiomyopathy have been observed. However, these side effects have not been reported with the low doses of cyclophosphamide that will be used in this study. With standard -dose cyclo phosphamide, secondary leukemia and myelodysplastic syndrome have also been reported as rare late occurrences . Allergic and anaphylactic reactions to cyclophosphamid e have been reported. In addition, rare cases of Stevens -Johnson syndrome/toxic epidermal necrolysis have occurred. A single dose of cyclophosphamide given 3 weeks prior to prostatectomy is not anticipated to cause side -effects t hat would potentially delay surgery or negatively affect the outcomes of surgery. 6.2.5 Treatment Modifications and Dosing Delays Since only a single dose of cyclophosphamide will be administered to each patient (arm B only) , dose modifications or treatmen t delays will not be permitted. 6.2.6 Supportive Care and Concomitant Medications Nausea/ vomiting: Low -dose cyclophosphamide does not typically induce nausea or vomiting. However, prochlorperazine may be given for this indication at a dose of 10 mg by mou th or intravenously as frequently as every 6 hours. Oral or intravenous corticosteroid are not permitted . However, prophylactic antiemetic therapy at the discretion of the treating physician is allowed. Durin g treatment (and for at least 60 minutes afterwa rds), patients should be observed for adverse reactions. Treatment facilities should have ACLS -certified personnel on site, as well as access to appropriate supportive care modalities including but not limited to oxygen administration, corticosteroids, ant ihistamines and catecholamines. Any or all of these modalities may be used in the case of hypersensitivity reactions or anaphylactic reactions. The following medications should generally be taken with caution by patients on chronic cyclophosphamide: allopurinol, cyclosporine, etanercept, ondansetron, hydrochlorothiazide, nevirapine, pentostatin, St John’s wort, tamoxifen, warfarin, and trastuzumab . In the present study, because only a single administration of low -dose cyclophosphamide will b e given , these m edications are not prohibited. However, the Principal Investigator should be notified if a patient is ta king any of these listed agents. 6.3 Degarelix Acetate 6.3.1 Dosage and Schedule Degarelix will be given in the outpatient setting as three 80 mg subcutaneous injections, for a total dose of 240 mg, approximately 2 weeks prior to radical prostatectomy. It will be give n to patients in both treatment arms, A and B . Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 34 of 68 J1265 PROT (Vers) 1.4 113012 6.3.2 Formulation and Preparation Degarelix is supplied as a powder for subcutaneo us injection. One vial of degarelix contains 80 mg of degarelix. Each vi al is to be reconstituted with 2 mL of sterile water for injection , USP . 2 mL is withdrawn to deliver 80 mg degarelix at a concentration of 40 mg/mL. One dose of degarelix comprises 240 mg given as three 2 mL injections of 80 mg each. 6.3.3 Drug Administration Degarelix is administered as a subcutaneous injection in the abdominal region. As with other drugs administered by subcutaneous injection, the injection site should vary periodic ally. Injections should be given in areas of the abdomen that will not be exposed to pressure, e.g. not close to waistband or belt. Degarelix is supplied as a powder to be reconstituted with sterile water for injection, USP. The reconstitution procedure ne eds to be carefully followed.