9.2.7.1 Collection of Specime n(s): Whole blood will be collected into heparinized tubes. 9.2.7.2 Handling of Specimen(s): Samples will be collected at room temperature and shipped to the CITN Central Laboratory the same day as the blood draw, so that the sample is received at the Central Lab oratory within 24 hours of blood draw. 9.2.7.3 Shipping of Specimen(s): Samples will be shipped at ambient temperature for overnight FEDEX delivery. Clinical research sites will utilize a web -based specimen tracking system (BSI -II) to communicate with the CITN Central Laboratory. The Central Laboratory will subsequently ship batched plasma samples to the assay site. 9.2.7.4 Site(s) Performing Correlative Study : The Kyn/Trp analysis will be conducted at Incyte Corporation , Wilmington, Delaware. 9.3 Special Studies: Immunogenicity Testing The formation of anti -drug antibodies (ADA) and neutralizing anti -drug antibodies (NADA) to glyco -rhIL-7 (CYT107) will be evaluated at: Pre -treatment with IL -7 (CYT107), and Week 11 (Day 70). If positive at Week 11 (Day 70), immun ogenicity testing will be re peated at the end of the study. 9.3.1 Collection of specimen(s): Whole blood will be collected into a Lithium Heparin tube. Samples will be centrifuged within 15 minutes and the plasma aliquoted into at least two vials . Please refer to the CITN -12-03 Laboratory Manual . NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 37 9.3.2 Handling of specimen(s): Plasma will be frozen at -80C and stored until shipped to the CITN Central Laboratory, Seattle, WA. 9.3.3 Shipping of Specimen(s): Samples will be packed on dry ice and shipped for ove rnight FEDEX delivery to the CITN Central Laboratory, Seattle, WA. 9.3.4 Site(s) Performing Immunogenicity Testing: RevImmune, Inc. , Bethesda , Maryland will perform both ELISA Binding (non -neutralizing) and neutralizing antibody assays according to their Stand ard Operating Procedure. 9.4 Sample Storage PBMC, serum, and plasma that remain after conducting the above -described correlative assays will be saved for future ancillary studies (e.g. soluble IL -7 receptor levels ). Residual cell pellets from whole blood processing (that would otherwise be discarded) will be stored for the possibility of isolating genomic DNA and conducting IL -7 receptor polymorphism analyses, should funding become available. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 38 10. STUDY CALENDAR Baseline evaluations are to be conducted following the last dose of sipuleucel -T, but prior to the first CYT107 injection . In the event that the patient’s condition is deteriorating, laboratory evalua tions should be repeated within 48 hours prior to initiation of the next CYT107 administration. Pre-study Pre-IL7 Week 1 Week 2 *(f) Week 3 Week 4 *(f) Week 6 Week 11 Week 23 Week 53 Off Study *(d) Within 7 days of receiving CYT1 07 Day 0 Day 7 ± 2 days Day 14 ± 2 days Day 21 ± 2 days Day 35 ± 2 days Day 70 ± 7 days Day 154 ±14 days Day 365 ±14 days CYT107 *(A) X X X X Sipuleucel -T (Provenge®) *(B) Standard Sip-T X Informed consent X Demographics X Medical history X Concomitant medications X X X X X X X X X X Physical exam X X X X X X X X X X Vital signs X X*(e) X*(e) X*(e) X*(e) X X X X X Height X Weight X X X X X X X X X X Performance status X X X X X X X X X X CBC w/diff, plts X X X X X X X X X Serum chemistry *(a) X X X X X X X X X Anti-nuclear antibody (ANA) X X CYT107 immunogenicity (ADA) assay *(b) X X X Adverse event evaluation X X X X X X X X X X Tumor measurements Within 45 days Tumor measurements are repeated every 12 weeks . Documentation (radiologic) must be provided for patients removed from study for progressive disease. X CT, MRI or PET of chest, abdomen, pelvis *(c) Within 45 days Documentation (radiologic) must be provided for patients removed from study for progressive disease. X NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 39 Pre-study Pre-IL7 Week 1 Week 2 *(f) Week 3 Week 4 *(f) Week 6 Week 11 Week 23 Week 53 Off Study *(d) Within 7 days of receiving CYT1 07 Day 0 Day 7 ± 2 days Day 14 ± 2 days Day 21 ± 2 days Day 35 ± 2 days Day 70 ± 7 days Day 154 ±14 days Day 365 ±14 days CT or MRI Brain (as indicated) *(c) Documentation (radiologic) must be provided for patients with symptoms X Bone scan *(c) Within 45 days Radiologic measurements should be performed every 12 weeks X EBV serostatus X X CMV serostatus X X PSA measurement X X X X X CTC X X IFNg ELISPOT X X X X X Proliferation assay X X X X X PBMC and T cell subset quantitation X X X X X PAP Ab, PA2024 ELISA X X X X X TREC detection X X X X TCR deep sequencing X X Kyn/Trp ratio X X X X X X *(A): CYT107; Dose as assigned; administration schedule. *(B): Sipuleucel -T (Provenge®); Dose as assigned; administration schedule. Standard Provenge® therapy (3 vaccinations) required prior to study entry. *(a): Serum chemistries include: Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium , chloride, creatinine, glucose, phosphorus, potassium, total protein, SGOT [AST], SGPT [ALT], sodium. *(b): CYT107 ADA testing will be repeated if positive at week 11 (Day 70 ± 7 days). Frozen plasma is required. *(c): CT, MRI or PET within 45 days ( 14 days preferred) is acceptable for imaging assessment purposes *(d): Off -study evaluation *(e): Vital signs will be repeated every 2 hours during the 4 hours observation period required after each injection of CYT107 (coh ort 2 only). *(f): Optional study visit for patients assigned to observation (cohort 1) NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 40 11. MEASUREMENT OF EFFEC T 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. Assessment of the primary endpoint is described in Sections 2.5 and 9.2. One secondary endpoint is an assessment of the clinical efficacy of sipuleucel -T plus CYT107 compared to sipuleucel -T alone. To assess clinical efficacy the protocol will assess differences in (1) overall survival, (2) PSA kinetics (3) progression free survival and, (4) circulating tumor cells (CTC). 11.1 Overall Survival Sipuleucel -T was approved by the FDA in men who have mCRPC with no or minimal symptoms due to a prolongation of median overall survival by 4.1 months compared with results in those treated with placebo . The protocol is not powered to dis cern modest effects on overall survival.