However, data on overall survival will be collected and analyzed. Patients will not be formally followed on protocol after week 53; however, data on OS will be collected and reported. 11.2 PSA Kinetics In the pivotal trials, sipuleucel -T induced no substantial differences in PSA reductions. However, the rate of the PSA increase was slower in patients who received the vaccine in another double - blind, randomized, placebo -controlled study (P -11) of 176 men with rising PSA after prostatectomy receiving hormonal therapy followed by vaccine or control [ Beer, 2007 ]. The PSADT was calculated from day 90 after vaccine to biochemical recurrence. Patients will have PSA measurements on weeks 1, 6, 11, 23, and 53. The presumption is that immune response will not have immediate effects but will require a period of time to induce an effect on PSADT, if it occurs. Thus, for trial analysis PSADT will arbitrarily be calculated from week 11 to week 23, and 53 or until new therapeutic intervention is initiated, whichever comes first. The PSADT will be evaluated according to the recommendations from PSA Working Group (PSAWG) [ Arlen, 2008 ]. 11.3 Progression free survival There was no discernable prolongation of progression free survival in the pivotal trial. However, if the addition of CYT107 substantially increases the immune response to PAP, it is possible that differences in progression free survival will be observed. PFS is defined as the duration of time from start of treatment to time of radiographic progression or death, whichever occurs first. PFS will consider both measurable disease and unmeasurable bony metastasis. Measurable disease will be measured by RECIST 1.1 criteria [ Eisenhauer, 2009 ]. Unmeasurable bony metastasis will be measured by radiographic criteria [ Scher, 2008 ]. PFS is not the primary endpoint. Thus, responses will not pro forma be re viewed by an expert(s) independent of the study at the study’s completion. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 41 11.4 Circulating Tumor Cells Circulating tumor cells (CTC) will be enumerated by the approved Veridex assay as exploratory analysis. 11.5 Measurement of Disease For the purposes of this study, baseline scans must be done within 45 days prior to beginning treatment (14 days preferred). Scans can be done before or after sipuleucel -T given that sipuleucel - T is not likely to have induced remissions. In addition to the patient’s baseline scan, tumor measurements are repeated every 12 weeks post therapy or per institutional standard of care. Response and progression for purpose of reporting data and publication will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [ Eisenhauer, 2009 ]. Duration of Response Duration of overall response : The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. Duration of stable disease : Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements. Measurable disease : Measurabl e lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm by chest x -ray or as >10 mm with CT scan, MRI, or calipers by clinical exam. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). Note: Tumor lesions that are situated in a previously irradiated area might or might not be considered measurable. Malignant lymph nodes : To be considered pathologically enlarged and measurable, a lymph node must be >15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At baseline and in follow -up, only the short axis will be measured and followed. Note : Cystic lesions that meet the criteria for radio graphically defined simple cysts should not be considered as malignant lesions (neither measurable nor non -measurable) since they are, by definition, simple cysts. ‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesi ons, if they meet the definition of measurability described above. However, if non -cystic lesions are present in the same patient, these are preferred for selection as target lesions. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 42 Target lesions : All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, representative of all involved organs, should be identified as target lesions and recorded and measured at baseline. Target lesions should be selected on the basis of t heir size (lesions with the longest diameter), be representative of all involved organs, but in addition should be those that lend themselves to reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does not lend itse lf to reproducible measurement in which circumstance the next largest lesion which can be measured reproducibly should be selected. A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculat ed and reported as the baseline sum diameters. If lymph nodes are to be included in the sum, then only the short axis is added into the sum. The baseline sum diameters will be used as reference to further characterize any objective tumor regression in the measurable dimension of the disease. Non-target lesions : All other lesions (or sites of disease) including any measurable lesions over and above the 5 target lesions should be identified as non-target lesions and should also be recorded at baseline. Measur ements of these lesions are not required, but the presence, absence, or in rare cases unequivocal progression of each should be noted throughout follow -up. 11.5.1 Methods for Evaluation of Measurable Disease All measurements should be taken and recorded in metr ic notation using a ruler or calipers. All baseline evaluations should be performed within 7 days from the beginning of treatment. The same method of assessment and the same technique should be used to characterize each identified and reported lesion at ba seline and during follow -up. Imaging -based evaluation is preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be imaged but are assessable by clinical exam. Clinical lesions : Clinical lesions will only be considered measurable when they are superficial ( e.g., skin nodules and palpable lymph nodes) and 10 mm diameter as assessed using calipers ( e.g., skin nodules). In the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended. Chest x -ray: Lesions on chest x -ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable. Conventional CT and MRI : This guideline has defined measurability of lesions on CT scan based on the assumption that CT slice thickness is 5 mm or less. If CT scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness. MRI is also acceptable in certain situations ( e.g. for body scans). Use of MRI remains a complex issue. MRI has excellent contrast, spatial, and temporal resolution; however, there are many image acquisition variables involved in MRI, which greatly impact image quality, lesion conspicuity, and measurement. Furthermore, the availability of MRI is variable globally. As with CT, if an MRI is performed, the technical specif ications of the scanning sequences used should be optimized for the evaluation of the type and site of disease. Furthermore, as with CT, the modality used at follow -up should be the same as was used at baseline and the lesions should be measured/assessed o n the same pulse sequence. It is beyond the scope of the RECIST guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body parts, and diseases. Ideally, the same type of scanner should be used and the image acquisition NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 43 protocol should be followed as closely as possible to prior scans. Body scans should be performed with breath -hold scanning techniques, if possible. PET-CT: At present, the low dose or attenuation correction CT portion of a combined PET -CT is not always of optimal diagnostic CT quality for use with RECIST measurements. However, if the site can document that the CT performed as part of a PET -CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then the CT portion of the PET -CT can be used for RECIST measurements and can be used interchangeably with conventional CT in accurately measuring cancer lesions over time. Note, however, that the PET portion of the CT introduces additional data which may bias an investigator if it is not routin ely or serially performed. Ultrasound : Ultrasound is not useful in assessment of lesion size and should not be used as a method of measurement. Ultrasound examinations cannot be reproduced in their entirety for independent review at a later date and, bec ause they are operator dependent, it cannot be guaranteed that the same technique and measurements will be taken from one assessment to the next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or MRI is advised. If there is concern about radiation exposure at CT, MRI may be used instead of CT in selected instances. Endoscopy, Laparoscopy : The utilization of these techniques for objective tumor evaluation is not advised. However, such techniques may be useful to confirm complete pathological response when biopsies are obtained or to determine relapse in trials where recurrence following complete response (CR) or surgical resection is an endpoint. Tumor markers : PSA alone cannot be used to assess response. If marke rs are initially above the upper normal limit, they must normalize for a patient to be considered in complete clinical response. Cytology, Histology : These techniques can be used to differentiate between partial responses (PR) and complete responses (CR ) in rare cases ( e.g., residual lesions in tumor types, such as germ cell tumors, where known residual benign tumors can remain). The cytological confirmation of the neoplastic origin of any effusion that appears or worsens during treatment when the measur able tumor has met criteria for response or stable disease is mandatory to differentiate between response or stable disease (an effusion may be a side effect of the treatment) and progressive disease. FDG -PET: FDG -PET usually not used in prostate cancer. However, rarely it might be reasonable to incorporate the use of FDG -PET scanning to complement CT scanning in assessment of progression (particularly possible 'new' disease). New lesions on the basis of FDG -PET imaging can be identified according to the following algorithm: a. Negative FDG -PET at baseline, with a positive FDG -PET at follow -up is a sign of PD based on a new lesion. b. No FDG -PET at baseline and a positive FDG -PET at follow -up: If the positive FDG -PET at follow -up corresponds to a new site of di sease confirmed by CT, this is PD. If the positive FDG - PET at follow -up is not confirmed as a new site of disease on CT, additional follow -up CT scans are needed to determine if there is truly progression occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG -PET scan). If the positive FDG -PET at follow -up NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 44 corresponds to a pre -existing site of disease on CT that is not progressing on the basis of the anatomic images, this is not PD. c. FDG -PET may be used to upgrade a respo nse to a CR in a manner similar to a biopsy in cases where a residual radiographic abnormality is thought to represent fibrosis or scarring. The use of FDG -PET in this circumstance should be prospectively described in the protocol and supported by disease -specific medical literature for the indication. However, it must be acknowledged that both approaches may lead to false positive CR due to limitations of FDG -PET and biopsy resolution/sensitivity. Note: A ‘positive’ FDG -PET scan lesion means one which is FDG avid with an uptake greater than twice that of the surrounding tissue on the attenuation corrected image. 11.5.2 Response Criteria: Evaluation of Target Lesions Complete Response (CR) : Disappearance of all target lesions. Any pathological lymph nodes (whether target or non -target) must have reduction in short axis to <10 mm. Partial Response (PR) : At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) : At le ast a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD) : Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference th e smallest sum diameters while on study. 11.6 Radiologic Progression -Free Survival of Bony Metastasis Radiographic progression -free survival is based on parameters suggested by Prostate Cancer Working Group 2 [ Scher, 2008 ]. A patient is considered to have progressed by bone scan if one of the following occurs after randomization: 11.6.1 The first bone scan with ≥2 new lesions compared to baseline is observed <12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline). 11.6.2 The first bone scan with ≥2 new lesions compared to baseline is observed ≥12 weeks from randomization and the new lesions are verified on the next bone scan ≥ 6 weeks later (a total of ≥2 new lesions compared to baseline). NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 45 11.7 Evaluation of Best Overall Response The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best r esponse assignment will depend on the achievement of both measurement and confirmation criteria. For Patients with Measurable Disease ( i.e., Target Disease) Target Lesion s Non-Target Lesions New Lesio ns Overall Resp onse Best Overall Response when Confirm ation is Required* CR CR No CR >4 wks. Confirmation** CR Non-CR/Non -PD No PR >4 wks. Confirmation** CR Not evaluated No PR PR Non-CR/Non - PD/not evaluated No PR SD Non-CR/Non - PD/not evaluated No SD Documented at least once >4 wks. from baseline** PD Any Yes or No PD no prior SD, PR or CR Any PD*** Yes or No PD Any Any Yes PD * See RECIST 1.1 manuscript [16] for further details on what is evidence of a new lesion. ** Only for non -randomized trials with response as primary endpoint. *** In exceptional circumstances, unequivocal progression in non -target lesions may be accepted as disease progression. Note : Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time should be reported as “ symptomatic deterioration.” Every effort should be made to document the objective progression even after discontinuation of treatment. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 46 For Patients with Non -Measurable Disease ( i.e., Non -Target Disease) Non-Target Lesions New Lesions Overall Response CR No CR Non-CR/non -PD No Non-CR/non -PD* Not all evaluated No not evaluated Unequivocal PD Yes or No PD Any Yes PD * ‘Non -CR/non -PD’ is preferred over ‘stable disease’ for non -target disease since SD is increasingly used as an endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised 12. DATA REPORTING / REG ULATORY REQUIREMENTS Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 8.0 (Adverse Events: List and Reporting Requirements). 12.1 Data Reporting 12.1.1 Method Data collection for this study will be done exclusively through Medidata Rave. Access to the trial in Rave is granted through the iMedidata application to all persons with the appropriate Rave roles in the CTSU Regulatory Support System (RSS). To access iM edidata/Rave the site user must have an active CTEP IAM account (https://eapps -ctep.nci.nih.gov/iam). In addition, site users that are members of the CITN must have the appropriate Rave roles (Rave CRA, Site PI, or Site co -PI) in RSS at the enrolling site. Upon initial site registration approval for the study in RSS, all persons with Rave roles assigned on the CITN roster will be sent a study invitation e -mail from iMedidata. To accept the invitation, site users must log into the Select Login (https://logi n.imedidata.com/selectlogin) using their CTEP -IAM user name and password, and click on the “accept” link in the upper right corner of the iMedidata page. Please note, site users will not be able to access the study in Rave until all required Medidata and s tudy specific trainings are completed. Trainings will be in the form of electronic learnings (eLearnings), and can be accessed by clicking on the link in the upper right pane of the iMedidata screen. Users who have not previously activated their iMedidata /Rave accounts at the time of initial site registration approval for the study in RSS will also receive a separate invitation from iMedidata to activate their account. Account activation instructions are located on the CTSU website, Rave tab under the Rave resource materials (Medidata Account Activation and Study Invitation Acceptance). Additional information on iMedidata/Rave is available on the CTSU website under the Rave tab at www.ctsu.org/RAVE/ or by contacting the CTSU Help Desk at 1 -888- 823-5923 or b y e-mail at ctsucontact@westat.com . NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 47 12.1.2 Responsibility for Data Submission This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0. Cumulative protocol - and patient -specific CDUS data will be submitted electronically to CTEP on a quarterly basis, either by FTP burst of data or via the CDS web application. This is the responsibility of the CITN COSC (Central Operating and Statistical Center). Reports are due January 31, April 30, July 3 1, and October 31. Instructions for submitting data using the CDUS can be found on the CTEP Web site (http://ctep.cancer.gov/reporting/cdus.html). The Coordinating Center is responsible for compiling and submitting CDUS data to CTEP for all participants and for providing the data to the Principal Investigator for review. When setting the dates, allow time for Coordinating Center compilation, Princ ipal Investigator review, and timely submission to CTEP by the quarterly deadlines (see Section 13.1.1). 12.2 CTEP Multicenter Guidelines This protocol will adhere to the policies and requirements of the CTEP Multicenter Guidelines. The specific responsibilities of the Principal Investigator and the Coordinating Center and the procedures for auditing are presented in Appendix B .  The Coordinating Center is responsible for distributing all IND Action Letters or Safety Reports received from CTEP to all participating institutions for submission to their individual IRBs for action as required. 12.3 Collaborative A greements Language: N/A 13. STATISTICAL CONSIDER ATIONS 13.1 Study Design/Endpoints The proposed clinical trial is a phase II, open -label, multicenter, randomized study of the administration of CYT107 after the completion of standard FDA -approved therapy with sipuleucel - T for patients with asymptomatic or minimally symptomatic mCRPC. Pati ents who have completed a standard course of sipuleucel -T will be randomly assigned to either observation or 10 μg/kg of subcutaneous CYT107 every week for 4 doses beginning 3 to 7 days after completing sipuleucel -T therapy. Day 0 is the day of the first i njection of CYT107. The first six patients randomly assigned to receive CYT107 will be followed for an additional 4 weeks prior to the study expanding past six patients, as a lead -in phase to ensure safety and tolerability of the selected CYT107 dose. Treatment Schema Cohort CYT107 Dose Frequency 1 - Observation No CYT107 dose -------- 2 - CYT107 10 μg/kg Days 0, 7 , 14 and 2 1 NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 48 IL-7 is expected to increase the peak and the persistence of the immune response. The persistence might be the most important for effective immunotherapy, i.e. increasing the “area under the curve”. Thus, the primary endpoint for sizing the trial will be quantification of T -cell responses to PA2024 measured at day 70 (week 11), 7 weeks after the last CYT107 injection. T cell responses will be measured by interferon -gamma ELISPOT as the most quantifiabl y and reproducible assay. In the IMPACT study, 2 weeks after last sipuleucel -T administration, the background -subtracted mean PA2024 ELISPOT was 40 SFC/ 3x105 PBMC with a standard deviation of 69 based on n = 63. At 10 weeks after the last administration the background - subtr acted mean PA2024 ELISPOT was 23 SFC/ 3x105 PBMC with a standard deviation of 36 based on n = 42. Participant leuk apheresis samples from pre - and post -Provenge® vaccine will be used when possible to allow planned a more comprehensive evaluation of longitud inal vaccine responses. Primary Endpoint: With 3 8 patients per group with evaluable data ( 40 patients per group, assuming 5% missing immunogenicity data), there is 80% power to detect a difference between a mean of 47 in the sipuleucel -T plus CYT107 grou p and a mean of 23 in the sipuleucel -T alone group, assuming the same standard deviation of 36 in both groups. This calculation is based on a two -sided t -test with a significance level of 0.05. The presumption is that the effect of CYT107 will be positive on all of the immune parameters and that the effect on each assay will track with positive effects on the other immune assays such that there should be similar power to detect differences in the other endpoints. These, however, are not considered primary e ndpoints, and hence no multiplicity adjustment will be made. The Mann -Whitney -Wilcoxon (MWW) Test will be used as part of the statistical analysis; the power is roughly equivalent to that based on the t -test. The effect of CYT107 will also be positive on c linical activity, but the results are likely to be more variable. 13.2 Sample Size/Accrual Rate 80 patients total will be enrolled in this study, 6-8 patients per month accrual total at approximately 12 CITN sites. Patients without adequate sampling for immune responses will be replaced . Accrual Targets Ethnic Category Sex/Gender Males Total Hispanic or Latino + 15 = 15 Not Hispanic or Latino + 65 = 65 Ethnic Category: Total of all subjects + 80 (B1) = 80 (C1) Racial Category American Indian or Alaskan Native + 12 = 12 Asian + 8 = 8 Black or African American + 31 = 31 Native Hawaiian or other Pacific Islander + 8 = 8 White + 21 = 21 Racial Category: Total of all subjects + 80 (B2) = 80 (C2) NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 49 13.3 Stratification Factors Patients will be stratified for prior abiraterone or neo-adjuvant chemotherapy with or without abiraterone in order to balance arms. 13.4 Analysis of Secondary Endpoints 1. To determine whether CYT107 administration increases the vaccine -induced antigen -specif ic T- cell immune response to PAP The effect on antigen -specific T -cell immune responses to PAP will be measured using the same assays and time points as for the primary endpoint, PA2024. 2. To assess the character of the T -cell immune response to PAP and PA2 024 The effect on the number and percentage of PBMC subsets and T lymphocyte subsets (i.e., CD4+ and CD8+ T cell naïve, effector memory, and central memory subsets, CD4+ Treg and activated CD4+ and CD8+ T cells) will be assessed using multiparameter flow cytometric analysis of whole blood. The PBMC immunophenotyping assay will quantify the absolute number and proportion of T cells (both CD8+ and CD4+), NK cells (CD56+CD3 -), NKT cells (CD56+CD3+), B cells (CD19+), monocytes (CD16+), dendritic cells (H LA-DR+ CD123+ or CD11c+), and CD122 (IL15R -beta) -expressing cells. An additional panel will quantify the absolute number and proportion of memory and naïve T cell subsets using antibodies to CD45RA, CCR7 and CD28 of regulatory T cells using antibodies to CD127 and CD25, and the activation state of T cells using antibodies to PD -1, ICOS, and HLA -DR, among others. The absolute change in each parameter as well as variance in change over time for each patient (mean, median, and SE/SD) will be evaluated. 3. To de termine whether CYT107 administration increases the vaccine -induced antigen -specific antibody immune response s to PAP and PA2024 IgM and IgG response to PAP and PA2024 will be measured by standard ELISA. 4. To quantify the effects of CYT107 on T -cell divers ity The T -cell repertoire will be characterized by T -cell receptor (TCR) deep sequencing and the analysis will be done with the Immunoseq Analyzer software (Harlan Robins, PhD, with Adaptive Biotechnologies, Seattle). 5. To assess the effects of CYT107 on t he immune competence of patients with advanced prostate cancer Bystander antigen specific immune responses will be assessed to other ongoing and nascent antitumor responses (e.g., PRAME, NY -ESO -1 and /or p53), additional tumor antigens specific to prostate cancer (e.g., PSA and /or PSMA), and memory viral responses (influenza A and CEF) using the IFNg ELISPOT assay. Thymic function will be assessed by measuring levels of T -cell receptor rearrangement DNA excision circles (TRECs). NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 50 6. To assess the clinical effi cacy and tolerability of sipuleucel -T plus CYT107 compared with sipuleucel -T alone Adverse events will be graded and reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Clinical efficacy will be assess differences in (1) overall survival, (2) PSA kinetics (3) progression free survival and, (4) circulating tumor cells (CTC). Progression free survival will be ass essed by RECIST criteria for measureable disease by bone scans and radiographic criteria for non -measurable bony metastasis. 13.5 Reporting and Exclusions 13.5.1 Evaluation of Toxicity All patients will be evaluable for toxicity from the time of their first treatment with CYT107. 13.5.2 Evaluation of Response All patients included in the study must be assessed for response to treatment, even if there are major protocol treatment deviations o r if they are ineligible. Each patient will be assigned one of the following categories: 1) complete response, 2) partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early d eath because of other cause, or 9) unknown (not assessable, insufficient data). [Note: By arbitrary convention, category 9 usually designates the “unknown” status of any type of data in a clinical database.] All of the patients who met the eligibility c riteria (with the possible exception of those who received no study medication) should be included in the main analysis of the response rate. Patients in response categories 4 -9 should be considered to have a treatment failure (disease progression). Thus , an incorrect treatment schedule or drug administration does not result in exclusion from the analysis of the response rate. Precise definitions for categories 4 -9 will be protocol specific. All conclusions should be based on all eligible patients. Su b analyses may then be performed on the basis of a subset of patients, excluding those for whom major protocol deviations have been identified ( e.g., early death due to other reasons, early discontinuation of treatment, major protocol violations, etc.). H owever, these sub analyses may not serve as the basis for drawing conclusions concerning treatment efficacy, and the reasons for excluding patients from the analysis should be clearly reported. The 95% confidence intervals should also be provided. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 51 REFERENCES Arlen PM, Bianco F, Dahut WL, D’Amico A, Figg WD, Freedland SJ, Gulley JL, Kantoff PW, Kattan MW, Lee A, Regan MM, Sartor O. Prostate -Specific Antigen Working Group’s Guidelines on PSA Doubling Time. J.