A P-value of ≤ 0.05 will be used to denote statistical significance. 10.5.2 Sample size calculation Our primary hypothesis is that men on the combination arm receiving cyclophosphamide/ GVAX in addition to ADT (arm B) will have a 100% or greater CD8+ T cell infiltration of the prostate than will men receiving ADT alone (arm A). A difference smaller than this in the primary endpoint would not be considered biologically meaningful. In the absence of any intervention, we have previously determined that the mean staining percentage for CD8+ T cells in tumor tissue is 0.42% ( standard deviation 0.36%) (Gurel and DeMarzo, unpublished data). We hypothesize that men on the control arm (arm A) would have similar CD8+ T cell staining percentages as those quoted above. In the combination arm (arm B), a biologically meaningful treatment effect would be achieved if prostatic CD8+ T cell responses were augmented by 100% or more compared to arm A. Therefore, with 16 patients per arm, and assuming an 86% coefficient of variation for the average CD8 area/spot area ratios, a one - sided 0.05 α -level t -test of the logarithms of these ratios would have 82% power to detect a 2-fold (100%) increase of CD8+ T cells in the degarelix plus cyclophosphamide/GVAX arm (arm B) compared to the deg arelix alone arm ( arm A). Treating Gleason score as a block factor reduces the variance, which would be adequate to offset the loss of power due to t he 1 degree of freedom associated with the blocking factor. In summary, 16 patients per arm will yield a total sample size of 32 men. With an estimated enrolment rate of 4 men per month, accrual is expected to last 8 months. 10.5.3 Stratification factors The randomization will be stratified by Gleason score: ≤7 vs 8- 10. 10.5.4 Statistical analysis of primary and secondary endpoints For a description of statistical methods used to evaluate the primary and secondary study outcomes, please see Section 10.2. 11. PROTECTION OF HUMAN SUBJECTS 11.1 Ethical Considerations This study will be conducted in compliance with the protocol, Good Clinical Practice ( GCP ) guidelines established by the International Conference on Harmoniz ation (ICH) , and the ethical standards set Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 54 of 68 J1265 PROT (Vers) 1.4 113012 forth in the Declaration of Helsinki of 2004 (these documents may be found at www.wma.net/e/policy/b3.htm and www.laakariliitto.fi/e/ethics/helsinki.html ). Review of this protocol by the Institutional Review Board (IRB)/Ethics Committee (EC), and the performance of all aspects of the study including acquisition of informed consent, must also be in accordance w ith the principles elaborated in the Declaration, as well as the ICH guidelines (Code of Federal Regulations (CFR), Title 21: Part 50 and Part 312). The p rincipal investigator will be responsible for submitting documents to the IRB/EC, and obtaining writte n approval for the protocol prior to st udy initiation. The approval of both the protocol and the informed consent must specify the date of approval, protocol number and version, and amendment number. The principal investigator is also responsible for notif ying the IRB/EC of any serious deviations from the protocol, or other circumstances that may result in added risk to participating patients . 11.2 Protocol Amendments Before starting the study, the p rotocol must be approved by the IRB/EC , the JHU Institutio nal Biosafety Committee ( IBC), the FDA , and the Recombin ant DNA Advisory Committee ( RAC ). Amendments to the protocol are subject to IRB approval before instituting. Any amendments made after IRB/EC approval is granted must be resubmitted to the IRB/EC for new approval. 11.3 Written Informed Consent Before obtaining consent, members of the study team must review the rationale for the treatment program with the patient. The discussion will review the alternatives available , the potential benefits of this prog ram, the risks and the probability of their occurrence, and the procedures to minimize these risks. Should an adverse event occur, the provisions available to ensure medical intervention must also be reviewed. Why the risks are reasonable in relation to the anticipated benefits, incentives, or costs that will/may be incurred as a result of participating in the study, as well as the efforts t o maintain confidentiality, should also be discussed with the patient. Patients will be required to sign and date (in triplicate) a statement of informed consent that meets the requirements of the Code of Federal Regulations (Federal Register Vol. 46, No. 17, January 27, 1981, part 50) and the IRB. The consent form should be submitted with the protocol for review and appr oval by the IRB/EC . The medical record should include a statement that written informed consent was obtained (and should document the date that it was obtained) before the patient is enrolled in the stu dy. The original signed consent document will become p art of the patient’s medical record , a copy will be forwarded to the project manager pursuant to registration, and a copy will be sent home with each patient. The consent form must include the following information : • the nature and objectives, potential toxicities, and benefits of the intended study • the length of therapy and follow -up required • alternatives to the proposed therapy (including standard and investigational therapies) • the name of the investigator(s) responsible for the protocol • the right of the patient to accept or refuse treatment and to withdraw from participation in the study at any time 11.4 Protection of Privacy Patients will be informed of the extent to which their confidential health information generated from this study may be used for re search purposes. After this discussion, they will be asked to sign a Notice of Privacy Practice research authorization/HIPAA form. This may be embedded within the informed consent document. The original signed documents will become part of the patient’s medical records, and each patient will receive a copy of the signed documents. The use and disclosure of protected health information will be limited to the individuals described in the research Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 55 of 68 J1265 PROT (Vers) 1.4 113012 authorization form. The research auth orization form must be prepared by the principal investigator and approved by the IRB. In compliance with US federal regulations, the investigator is required to permit representatives of the US Food and D rug Administration (FDA) or other regulatory authorities to review and/or copy any medical records relevant to the study in accordance with local laws. Patients will be informed of the extent to which their confidential health information generated from this study may be disseminated to other parties. Should direct access to med ical records require a waiver or authorization separate from the subject’s statement of informed consent, it is the responsibility of the investigator to obtain such permission in writing from the patient. 11.5 Study Termination or Modificatio n Adverse event s and laboratory data from this trial wi ll be assessed by the p rincipal investigator and/or medical monitor on an ongoing basis. At least quarterly , data from the clinical database will be reviewed. The results of this review will be shared wit h all investigators either in writing or as part of a teleconference. SAEs will be reviewed as they are reported to the principal investigator or project manager , and the medical monitor will make an assessment regarding the safety of continuing or modifyi ng the study. This assessment will be shared with the investigators either in writing or as part of a teleconference. Shoul d the assessment of either the principal investigator or the medical monitor be that the trial should be terminated, the study will t hen be closed to further accrual . Follow -up safety assessments will be performed for all patients who are taken out of the study prematurely. Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 56 of 68 J1265 PROT (Vers) 1.4 113012 12. REFERENCES 1.