A Randomized, Double-Blind Phase II Study of Sipuleucel-T (Provenge®) Followed by Indoximod or Placebo in the Treatment of Patients With Asymptomatic or Minimally Symptomatic Metastatic Castration Resistant Prostate Cancer
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Sponsor: Masonic Cancer Center, University of Minnesota

University of Minnesota 
Masonic Cancer Center  
Cancer Experimental Therapeutics Initiative (CETI) 
 
 
 
A Randomized, Double-Blind Phase II Study of Sipuleucel-T 
(Provenge®) Followed by Indoximod or Placebo in the Treatment 
of Patients with Asymptomatic or Minimally Symptomatic 
Metastatic Castration Resistant Prostate Cancer 
 
CPRC #:  2011LS109 
IND #:  114463 
 
University Of Minnesota 
 
IND Sponsor/Principal Investigator 
 
 Shilpa Gupta, MBBS 
 
Co-Investigators: 
Jeffrey S. Miller, MD  
Bruce R. Blazar, MD 
Gautam G. Jha, MBBS, MS 
Robert Kratzke, MD 
Christopher Warlick, MD, PhD 
Badrinath Konety, MD, MBA 
 
Biostatistician: 
Joseph Koopmeiners, PhD  
 
 
Medical College of Georgia 
David H. Munn, MD (pathology research collaborator) 
 
 
Participating Affiliate Institutions: 
 
University of Illnosis Cancer Center (PI:  Arkadiusz Dudek, MD) 
Weill Cornell Medical College (PI: Scott Tagawa, MD) 
Pennsylvania State University (PI: Sheldon Holder, MD) 
 
Version Date: 
September 30, 2015 
 
 
Confidential 

Sipuleucel-T Followed by Indoximod or Placebo in Castration Resistant Prostate Cancer 
 
 
 
 
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CPRC #2011LS109 
Key Contact Information 
Site 
Contact Information 
Role 
Masonic Cancer Center, 
University of Minnesota 
Shilpa Gupta, MBBS 
Masonic Cancer Center, University Of Minnesota 
MMC 480 Mayo   
420 Delaware St SE 
Minneapolis, MN 55455 
Email guptash@umn.edu 
Phone:  612 624-5620 
Pager:  612 899-4560 
Principal 
Investigator 
University of Illinois 
Cancer Center  
Arkadiusz Dudek, MD, PhD 
914 S. Wood Street  MCA 315 
Chicago, IL 60612 
Email:  adudek@ulc.edu 
Phone:  (312) 413-8878 
 
Site PI 
Weill Cornell Medical 
College 
Scott T. Tagawa, MD 
525 East 68th Street 
Starr 900 
New York, NY 10065 
Email:  stt2007@med.cornell.edu 
Phone:  (646) 962-2072 
Site PI 
Pennsylvania State 
University and 
Milton S. Hershey 
Medical Center 
Sheldon Holder, MD 
500 University Dr.  
Hershey, PA 17033 
Site PI 
Masonic Cancer Center, 
University of Minnesota 
Gautam G. Jha, MBBS, MS 
Email:  jhaxx014@umn.edu 
Pager:  612 899-9583 
IND Sponsor 
Medical College of 
Georgia 
David  H. Munn, MD 
Email:  dmunn@georgiahealth.edu 
Research Related 
Pathology 
 
 

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CPRC #2011LS109 
Revision History 
 
Revision 
# 
Version 
Date 
Details of changes 
Consent 
change? 
 
11/01/2011 Original to CPRC  
 
 
11/23/2011 
In response to CPRC deferral 
 
 
12/15/2011 In response to CPRC stipulations, original version to FDA  
12/15/2011 
 
02/08/2012 
In response to FDA initial review 
Streamline patient visits during 1-MT/study drug 
Permit Provenge to be given by local physician with the 
understanding that patient must sign consent at the study 
center and return to the study center the day after the 3rd 
Provenge infusion for blood collection and to start Study 
Drug; 
Other minor edits/clarifications 
02/08/2012 
1 
09/10/2012 
Replace 1-MT with newer name of indoximod throughout 
protocol including title; 
Add affiliate names and contact information;  
Update research related lab instruction; increase blood 
volume from 60 ml to 90 ml; add a 2nd baseline collection, 
move week 8 time point to week 10 to match schema; 
Section 8.3 – add SAE reporting to Dendreon and NewLink; 
minor edits throughout 
09/10/2012 
2 
10/15/2012 
Update dose of indoximod to 2400 mg in a divided dose 
twice a day as it represents the current phase II dosing  (the 
dose currently being used in clinical trials) – increase # of 
placebo capsules to match the new dose; 
Section 3.7 and appendix I - Relax baseline serum creatinine 
to < 2.0 mg/dL to align with other similar trials and lack of 
renal toxicity in either drug. 
 
10/15/2012 
3 
07/15/2013 
Schema and section 4.2 - Change randomization from at 
time of enrollment to week 4 
Schema and section 6.2  - Add to SOC - serum collection for 
circulating tumor cells (CTCs) at baseline and week 14 
Schema and section 6 - Permit 2nd baseline research blood 
sample to be drawn at any time prior to the first spiuleucel-T 
infusion 
Schema and section 6.2 - Separate research related serum 
collection (all patients) and tumor biopsy at pre and at week 
14 (optional requiring additional consent)  
Section 5.2.2 – clarify positive ANA must be > 5 times upper 
limit of normal before additional testing/treatment 
modification is required 
Title page and Key Contact Info - Update affiliates sites and 
investigators 
Other minor updates throughout protocol 
 
no changes 

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Revision 
# 
Version 
Date 
Details of changes 
Consent 
change? 
4 
09/02/2014 
Title page and Key Contact Info – update affiliate sites and 
investigators 
Section 3.7 and appendix I – delete ANC eligibility 
requirement, add CD4 count > 400 eligibility requirement if 
WBC </= 3,000 
Section 8.4 table - Update telephone number for Dendreon 
Corporation Serious Adverse Event reporting 
Update table of contents to show 2 levels of headings 
Other minor edits as tracked 
minor 
updates 
5 
03/10/2015 
Title page and Key Contact Info – update affiliate sites and 
investigators 
section 3.4 and checklist – change castration level of 
testosterone for </= 30 ng/dL to </= 50 ng/dL to be 
consistent with other studies; clarify several other criteria 
section 5.2 0 revise how the indoximod tablets are to be 
taken – with water on an empty stomach, previously with 
food acceptable 
section 5.2.1 – update indoximod adverse event section 
based on updated IB 
schema and section 6.1 – consent for optional biopsy to be 
included in main treatment consent; 
section 6.2 – add drug reconciliation to each visit 
section 7.1 updated indoximod/placebo packing information 
section 7.2 updated indoximod/placebo manufacturing 
information  
other minor edits as tracked 
Consent related changes – 
update risks of indoximod based on updated IB 
yes 
including 
merging of 
treatment 
and biopsy 
consents 
6 
9/30/2015 
Change Principal Investigator from Gautam Jha, MBBS to 
Shilpa Gupta, MBBS 
yes 
 
 
 

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Table of Contents 
 
 
Key Contact Information .................................................................................................... 2 
Revision History ................................................................................................................ 3 
Protocol Synopsis ............................................................................................................. 7 
Schema ............................................................................................................................. 8 
1 
Objectives .................................................................................................................. 9 
1.1 
Primary Objective ............................................................................................... 9 
1.2 
Secondary Objectives ......................................................................................... 9 
1.3 
Correlative Objectives ......................................................................................... 9 
2 
Background and Rationale ......................................................................................... 9 
2.1 
Prostate Cancer .................................................................................................. 9 
2.2 
Sipuleucel-T (Provenge) ................................................................................... 10 
2.3 
1-methyl-D-tryptophan (1-MT, indoximod) ........................................................ 10 
2.4 
Rationale ........................................................................................................... 11 
3 
Patient Selection ...................................................................................................... 12 
4 
Patient Registration/Randomization ......................................................................... 14 
4.1 
Registration with Masonic Cancer Center Clinical Trials Office ........................ 14 
4.2 
Patient Randomization ...................................................................................... 15 
4.3 
Patients Who Are Registered and Do Not Receive Study Treatment ............... 15 
5 
Treatment Plan ........................................................................................................ 15 
5.1 
Sipuleucel-T ...................................................................................................... 15 
5.2 
Indoximod/Placebo ........................................................................................... 17 
5.3 
Supportive Care ................................................................................................ 22 
5.4 
Duration of Indoximod/Placebo ......................................................................... 22 
5.5 
Duration of Study Participation ......................................................................... 23 
6 
Clinical Evaluations and Procedures ....................................................................... 23 
6.1 
Baseline and Post Treatment ........................................................................... 24 
6.2 
During Treatment .............................................................................................. 25 
7 
Study Drug (Indoximod/Placebo) Information .......................................................... 27 
7.1 
How Supplied .................................................................................................... 27 
7.2 
Manufacture and Control .................................................................................. 27 
7.3 
Drug Procurement ............................................................................................ 27 
7.4 
Drug Accountability ........................................................................................... 28 
7.5 
Breaking the Blind ............................................................................................. 29 
7.6 
Return/Destruction of Study Drug ..................................................................... 29 
8 
Adverse Event Documentation and Reporting ......................................................... 30 
8.1 
Definitions ......................................................................................................... 30 
8.2 
Adverse Event Documentation ......................................................................... 31 
8.3 
Required Reporting:  Affiliates to the Masonic Cancer Center ......................... 31 

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8.4 
U of MN Required Reporting: FDA, IRB, MCC’s SAE Coordinator, NewLink and 
Dendreon ..................................................................................................................... 32 
9 
Measurement of Effect ............................................................................................. 34 
9.1 
Immune Response to PA2024 .......................................................................... 34 
9.2 
Progression Free Survival ................................................................................ 34 
9.3 
PSA Progression .............................................................................................. 35 
9.4 
Imaging Progression ......................................................................................... 35 
10 Study Data Collection and Monitoring ...................................................................... 35 
10.1 
Data Management ............................................................................................ 35 
10.2 
Case Report Forms .......................................................................................... 35 
10.3 
Data and Safety Monitoring Plan (DSMP) ........................................................ 36 
10.4 
Monitoring ......................................................................................................... 36 
10.5 
Record Retention .............................................................................................. 37 
11 Study Endpoints ....................................................................................................... 37 
11.1 
Primary Endpoint .............................................................................................. 37 
11.2 
Secondary Endpoints ........................................................................................ 37 
12 Statistical Considerations ......................................................................................... 37 
12.1 
Power and Sample Size ................................................................................... 38 
12.2 
Early Termination for Excess Toxicity ............................................................... 38 
13 References ............................................................................................................... 39 
Appendix I – Eligibility Checklist ...................................................................................... 40 
Appendix II - Performance Status Scales ....................................................................... 42 
Appendix III – RECIST v 1.1 ........................................................................................... 43 
Appendix IV - Auto-Immune Symptom Evaluation Checklist .......................................... 47 
Appendix V – FACT P (version 4) ................................................................................... 48 

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Protocol Synopsis 
A Randomized, Double-Blind Phase II Study of Sipuleucel-T (Provenge®) 
Followed by Indoximod or Placebo in the Treatment of Patients with 
Asymptomatic or Minimally Symptomatic Metastatic Castration Resistant 
Prostate Cancer 
 
Study Design: 
This is a randomized, double blind, multi-institutional phase II therapeutic study 
of indoximod or placebo after the completion of standard of care sipuleucel-T 
(Provenge®) in men with asymptomatic or minimally symptomatic metastatic 
prostate cancer that is castration resistant (hormone refractory).  Patients are 
randomized to receive either twice daily oral indoximod or placebo for 6 
months beginning the day after the third and final sipuleucel-T infusion.   
 
Research related correlatives will include serial blood sampling for immune 
monitoring and an optional prostate or metastatic site biopsy at enrollment and 
at week 14. 
 
Primary Objective: 
To assess the augmentation of immune response to sipuleucel-T measured at 
14 weeks from first leukapheresis, in response to twice daily oral indoximod  at 
a dose of 2400 mg/day or an identical looking placebo  
 
Secondary 
Objectives: 
• To assess the safety of indoximod when administered post sipuleucel-T 
therapy 
• To assess efficacy as measured by improvement in time to disease 
progression, objective response rate, overall survival 
• To assess health related quality of life improvement on therapy 
 
Inclusion Criteria: 
 
 
 
 
 
 
 
Study Population: 
 
 
Sample Size: 
 
Duration of 
Treatment: 
• Metastatic castration resistant prostate cancer 
• Serum PSA ≥ 2.0 ng/ml at study enrollment  
• Planned standard of care treatment with sipuleucel-T 
• Asymptomatic or minimally symptomatic disease as demonstrated by 
ECOG Performance Status 0 or 1 and no need for opiate pain medications 
to control pain/symptoms 
• Adequate organ function within 14 days of study enrollment  
 
Men with asymptomatic or minimally symptomatic castration resistant prostatic 
adenocarcinoma 
 
Approximately 50 subjects will be enrolled (1:1 indoximod vs placebo) at up to 
5 sites 
 
Sipuleucel-T will be administered as standard of care either at the study center 
or by the referring physician.  Oral indoximod /placebo will be self-administered 
twice daily for 6 months starting after the last infusion of sipuleucel-T.  Patients 
will be treated for a minimum of 12 weeks of indoximod /placebo before 
disease progression can be declared and indoximod /placebo will not be 
discontinued for increasing PSA in the absence of symptomatic clinical 
progression.  
 

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Schema 
Enrollment Plan: 
Eligible, consenting patients will be enrolled to the study prior to the first leukapheresis (week 0).  
Randomization to either indoximod or placebo will occur at the beginning of week 4 (the week of 
the 3rd leukapheresis/sipuleucel-T infusion). 
 
 
 
Treatment Plan:  
 
                                                Indoximod/Placebo PO bid for 6 months 
 
Week      pre    0       2        4       6        10       14                            28                      follow for  
Immune      X      X                   X        X         X          X                                 X                
   survival 
Monitoring   
Biopsy                X                                                      X                    
(Optional) 
 
    Sipuleucel-T (Provenge®) - leukapheresis at weeks 0, 2, and 4 with sipuleucel-T infused 3 
days later per Standard of Care 
 
Indoximod 2400 mg/day or Placebo – begin 1 day after last sipuleucel-T infusion, continue 
twice daily for 6 months (24 weeks)  
 
Immune Monitoring/Indoximod Levels:  
1. At the time of screening/consent signature (1st baseline sample) 
2. Any time prior to the first sipuleucel-T infusion on week 0 (2nd baseline sample) 
3. After 3rd  sipuleucel-T infusion on week 4 
4. 2 weeks from initiation of treatment with indoximod/placebo on week 6 
5. 6 weeks from initiation of treatment with indoximod/placebo on week 10 
6. 10 weeks from initiation of treatment with indoximod/placebo on week 14 
7. 24 weeks from initiation of treatment with indoximod/placebo on week 28 
 
Immune Response Biomarkers - Serum Sample:  
1. Any time prior to the first sipuleucel-T infusion on week 0 
2. 10 weeks from initiation of treatment with indoximod/placebo on week 14 
 
Biopsy (optional): 
1. Prior to first leukapheresis on week 0 
2. 10 weeks from initiation of treatment with indoximod/placebo on week 14 
 

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1 
Objectives 
1.1 
Primary Objective 
The primary objective of this study is to assess the augmentation of 
immune response to sipuleucel-T measured at 14 weeks from first 
leukapheresis, in response to twice daily oral indoximod at dose of 2400 
mg/day or an identical looking placebo. 
 
1.2 
Secondary Objectives 
• To assess the safety of indoximod when administered post 
sipuleucel-T therapy 
• To assess efficacy as measured by improvement in time to disease 
progression, objective response rate, overall survival 
• To assess health related quality of life improvement on therapy 
 
1.3 
Correlative Objectives 
• To assess immune response at subsequent time points through 
week 28 and validate detection of PA2024 antibody response 
• To assess other immune monitoring data including 
immunophenotyping 
 
 
2 
Background and Rationale 
2.1 
Prostate Cancer 
Prostate cancer is the most common solid tumor malignancy in men in the 
United States.  It is estimated that 217,730 men will be diagnosed with 
and 32,050 men will die of cancer of the prostate in 2010.(1)The vast 
majority of men are diagnosed at a localized stage and treated with 
prostatectomy or radiation therapy.  While the overall five-year relative 
prostate cancer survival rate for 2001-2007 was 99.4 percent(1); 
approximately 1 in 3 men with early stage prostate cancer will experience 
a rise in the PSA levels within 5 years after initial treatment.  At this point 
androgen ablation either through surgical or medical castration is the 
standard treatment for metastatic or recurrent disease.  However this is 
only a temporary fix as most men who survive long enough (as the median 
age of diagnosis is 67 years) eventually develop castration resistant 
disease.  The offer of chemotherapy with docetaxel suggests a survival 
benefit, but due to the associated “quality of life” side effects (alopecia, 
fatigue, neutropenia, and neuropathy) most men with asymptomatic 
disease will delay treatment until symptomatic.  Thus, alternate treatment 
options are needed for this group of men with metastatic castration 

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resistant prostate cancer who, despite their disease maintain a good 
performance status with little or no disease associated symptoms. 
2.2 
Sipuleucel-T (Provenge) 
After decades of promise and research, sipuleucel-T (Provenge) has been 
the first vaccine therapy approved for treatment of any cancer in the 
United States. Sipuleucel-T involves ex-vivo sensitization of peripheral 
blood mononuclear cells to a custom prostatic acid phosphatase and 
granulocyte monocyte – colony stimulating factor (GM-CSF) fusion protein 
(PA 2024) followed by autologous transfusion. Sipuleucel-T is very well 
tolerated with mostly grade 2 side effects consistent with cytokine release. 
It has shown to improve survival by 3-4 months as compared to placebo in 
randomized, double blinded phase III clinical trials.(2, 3) Besides this 
modest improvement in survival, there has been no improvement in time 
to objective disease progression or an objective response rate (>25% 
decline in PSA).(2, 3) Although this has been a huge first stride in 
development of immunotherapies and first proof of principle, additional 
progress needs to be made before this technology has its fullest and most 
widely-applicable impact in treating cancers of prostate and other 
malignancies.  
2.3 
1-methyl-D-tryptophan (1-MT, indoximod) 
Indoleamine 2,3-dioxygenase (IDO) is a key immune-modulatory enzyme 
that degrades tryptophan to bioactive kynurenine metabolites. The 
process and effects of tryptophan depletion and kynurenine metabolism 
together form the immuno-modulatory IDO pathway(4), which promotes 
peripheral immune tolerance by direct inhibition of effector T cells, 
activation of pre-existing Foxp3+ Tregs, and conversion of naïve T cells to 
Tregs. 1-MT is a competitive inhibitor of the immunoregulatory enzyme, 
IDO, a critical regulator of immunosuppressive responses. 
 
In the preclinical studies, 1-MT was readily absorbed following oral 
administration in mice, rats, and dogs and the bio-availability ranged from 
85 to 100%(6). It was determined to be safe in rats and pigs at doses as 
high as 3000 mg/m2/day (500 mg/kg/day) administered for 4 weeks and no 
significant clinical, hematology or chemistry abnormalities were noted.  
In preclinical studies severity of toxoplasmosis was increased and 
activation of latent toxoplasmosis was noted in mice (unpublished data/7). 
Experimental colitis and encephalitis in preclinical studies were worsened 
by administration of 1-MT, although colitis and encephalitis have not been 
noted by administration of 1-MT alone. (8,9).  
 
Seventeen patients with advanced/metastatic solid tumors having 
progressed on established salvage therapy have been studied in phase I 
clinical trial at dose escalating from 200 mg once daily to 600 mg twice 
daily continued till disease progression or 3 months with 3 patients treated 

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at each dose level. Pharmacokinetics for 1-MT has been linear within this 
dose range (7). This has been well tolerated in the patient groups so far 
and most patients had only grade I or II toxicities consistent with advanced 
disease in a heavily pretreated population (7). The most frequently 
reported adverse events (regardless of attribution), occurring in ≥ 30% of 
patients, were fatigue, nausea and dyspnea (shortness of breath), muscle 
weakness (lower extremities), and pain in the lower extremities. The most 
frequently reported laboratory abnormalities (regardless of attribution), 
occurring 
in 
≥ 
30% 
of 
patients, 
were 
lymphopenia, 
anemia, 
hypoalbuminemia, hyperglycemia, hypokalemia, and hyponatremia. In the 
higher dose cohorts two cases of mild hypophysitis were noted during 
therapy with D-1MT which resolved on its own without any pharmacologic 
intervention. The most frequently observed adverse event which is 
possibly related to D-1MT is muscle weakness of the lower extremities 
(25%). Lymphopenia (43.75%) is the most frequently observed laboratory 
abnormality possibly related to 1-MT. There have been two CTCAE grade 
3 adverse events of hyponatremia and dizziness which were possibly 
related to 1-MT were reported. 
 
In a separate phase I dose-escalation study, 48 patients have been 
treated to a maximal dose of 2000 mg bid without attaining a MTD (7).  
The pharmacokinetics on this study was very similar to the earlier phase I 
study except that AUC values did not show a proportional increase with 
dose at the highest dose. This is in line with experience in rats and dogs 
where plasma concentrations of drug plateau due to finite intestinal 
absorptive area. Based on pharmacokinetics of indoximod tested in phase 
I trial, a dose of 1200 mg bid has been proposed for the phase II trials.  
Twelve patients have been treated at this dose of 1200 mg bid or higher in 
the phase I clinical trial without any notable toxicity.  Indoximod is currently 
being studied in an ongoing phase II clinical trial for patients with breast 
cancer at this dose of 1200 mg bid along with docetaxel. 
 
When indoximod (1-MT) used immediately post sipuleucel-T as in this 
clinical trial, it might increase the side effects of cytokine release from last 
infusion of sipuleucel-T. 
 
2.4 
Rationale 
It has long been established that the tumors cause local immune-
suppression that leads to tolerance toward various tumor antigens.  This is 
primarily mediated by a linked set of inhibitory mechanisms involving 
regulatory T cells (Tregs), which dominantly inhibit other T cells(5), and by 
inhibitory check-points including IDO, CTLA4 and PD-1. Vaccine therapy 
by itself is limited in its ability to overcome this anergy and 
immunosuppressive microenvironment, without somehow interrupting 
suppression by Tregs or one of the key inhibitory checkpoints. 
  

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The IDO pathway is an attractive target because it sits at a nexus between 
immunosuppressive checkpoint blockade and functional Treg inhibition.  In 
Phase I trials, 1MT has had little toxicity (especially in patients who have 
not received prior immunotherapy).  We hypothesize that inhibition of the 
IDO pathway by indoximod (1-MT) will permit a robust and possibly more 
sustained immune response to sipuleucel-T, which   may lead to further 
improvement of anti-cancer effects.  Importantly, preclinical mouse studies 
show that tumor-bearing hosts are primed to express high levels of IDO, 
and this host IDO actively suppresses anti-tumor T cell responses.  Thus, 
indoximod when combined with sipuleucel-T would primarily target the 
IDO expressed by the host, which inhibits optimal anti-tumor T cell 
responses to sipuleucel-T.  This means that it is not necessary or 
beneficial to screen patients for IDO expression in their tumors, or their 
sipuleucel-T preparation, because these are not the primary target of the 
therapy.   
 
In this randomized double blind phase II trial, indoximod or placebo will be 
administered following standard of care sipuleucel-T therapy to assess the 
augmentation of immune response to sipuleucel-T.  Indoximod /placebo 
will be self-administered orally twice daily starting after the last sipuleucel-
T infusion on week 4 (with first leukapheresis being week 0) and will be 
continued for 6 months in the absence of disease progression.  
 
We plan to offer trans-rectal biopsy of prostate prior to initiating therapy 
with sipuleucel-T and at 14 weeks from start of therapy for all patients who 
have an intact prostate and have not received radiation to the prostate. 
We will also offer biopsies to patients who have an easily accessible 
metastasis that can be biopsied before and after treatment. Biopsy of the 
primary tumor or metastatic site will help understand local immune 
response to treatment in individual patients. Simultaneous assessment of 
the immune response within the peripheral blood and within the tumor will 
help understand immune response to treatment and possibly establish 
markers of response. The information gained from this study would help 
devise strategies to better develop sipuleucel-T, indoximod and other 
immunotherapies for prostate cancer.  
 
 
3 
Patient Selection 
Study entry is open to adult men regardless of race or ethnic background.  
While there will be every effort to seek out and include minority patients, 
the patient population is expected to be similar to that of other prostate 
cancer studies at the University Of Minnesota and other participating 
institutions.  
 

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Patients with metastatic castration resistant prostate cancer with minimally 
symptomatic or asymptomatic disease (the clinical indication for use of 
sipuleucel-t) will be considered for enrollment in this clinical trial.  
 
Inclusion Criteria 
3.1 
Histologically documented adenocarcinoma of the prostate with 
metastatic disease as evidenced by soft tissue (e.g. lymphoid) 
and/or bony metastases on baseline CT scan of the abdomen and 
pelvis and/or bone scan   
3.2 
Castration-resistant based on a current or historical evidence of 
disease progression despite surgical or medical castration as 
demonstrated by one or more of the following: 
• PSA 
progression 
(defined 
as 
two 
consecutive 
PSA 
measurements at least 14 days apart ≥ 2.0 ng/ml and ≥ 50% 
above the minimum PSA during castration therapy or above 
pre-treatment value if no response)  
• progression of measurable disease based on RECIST (≥ 20% 
increase in the sum of the diameters of all target lesions or the 
development of any new lesions – appendix III) 
• progression of non-measureable disease based on imaging 
studies pre section 9.4 
3.3 
Serum PSA ≥ 2.0 ng/ml at study enrollment 
3.4 
Castration levels of testosterone defined as ≤ 50 ng/dL at study 
enrollment 
Must be at least 3 months from surgical castration or must have 
received medical castration therapy for at least 3 months and be 
receiving such therapy at the time of confirmed disease progression 
as defined in section 3.2 
3.5 
Asymptomatic or minimally symptomatic disease as demonstrated 
by ECOG Performance Status 0 or 1 (appendix II) and no need for 
opiate pain medications to control pain/symptoms 
3.6 
Age 18 years and older 
3.7 
Adequate bone marrow, renal and hepatic function within 14 days 
of study enrollment defined as: 
• Bone marrow: WBC >3,000/ mcL or CD4 count >400 cells/mm3; 
platelets >100,000/ mcL  
• Renal: creatinine <2.0 mg/dL OR creatinine clearance >60 
mL/min/1.73 m2  
• Hepatic: total bilirubin <1.5 X institutional ULN; AST(SGOT) and 
ALT(SGPT) <2.5 X institutional ULN 
3.8 
Voluntary written consent  
 
 

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Exclusion Criteria 
3.9 
Visceral metastases (e.g. lung, liver, brain, kidney, spleen) as the 
safety and efficacy of sipuleucel-T has not been established in this 
patient population 
3.10 Use of systemic corticosteroids or other immunosuppressive agents 
within the previous 4 weeks of study enrollment 
3.11 HIV-positive patients and those with other acquired/inherited 
immunodeficiency 
3.12 Active hepatitis including hepatitis B or C  
3.13 History of gastrointestinal disease causing malabsorption or 
obstruction such as, but not limited to Crohn’s disease, celiac 
sprue, tropical sprue, bacterial overgrowth/blind loop syndrome, 
gastric bypass surgery, strictures, adhesions, achalasia, bowel 
obstruction, or extensive small bowel resection 
3.14 Inability to take medications by mouth 
3.15 History of allergic reactions attributed to compounds of similar 
chemical or biologic composition of those used in this study 
3.16 Active autoimmune disease, chronic inflammatory condition, 
conditions 
requiring 
concurrent 
use 
of 
any 
systemic 
immunosuppressants or steroids. Mild-intermittent asthma requiring 
only occasional beta-agonist inhaler use or mild localized eczema 
will not be excluded. 
3.17 Previous allo-transplant of any kind 
3.18 History of prior treatment with anti-CTLA4 blocking antibody 
 
 
4 
Patient Registration/Randomization 
Registration will occur after the patient has signed the subject consent 
form and eligibility is confirmed, but before the 1st leukapheresis has been 
performed.   
 
To be eligible for registration to this study, the patient must meet each 
criteria listed on the eligibility checklist (appendix I) based on the eligibility 
assessment documented in the patient’s medical record.  A copy of the 
eligibility checklist is also under attachments within the study in The Online 
Enterprise Research Management Environment (OnCoreTM). 
4.1 
Registration with Masonic Cancer Center Clinical Trials Office 
Upon completion of the screening evaluation and obtaining written 
consent, the site study coordinator or designee will enroll the patient into 
OnCore.  A copy of the signed consent and completed eligibility checklist 
must be uploaded as an attachment under the patient record in OnCore. 

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CPRC #2011LS109 
 
OnCore will notify key study personnel of the registration via a system 
generated email. 
4.2 
Patients Who Are Registered and Do Not Receive Sipuleucel-T  
If a patient is registered to the study and is later found not able to begin 
sipuleucel-T, for whatever reason, he will be removed from study and 
treated at the physician’s discretion.  The patient will be considered a 
screen/baseline failure and the reason for removal from study will be 
clearly indicated in OnCore. 
4.3 
Patient Randomization  
Each site will do their own randomization through the institutional 
investigational pharmacist using a randomized packet provided by the 
study statistician at the time of study site activation.   
 
To be eligible for randomization a patient must have receive all 3 doses of 
spiuleucel-T.   
 
Patients will be randomized 1:1 to either indoximod or an identical looking 
placebo by notifying the institutional investigational pharmacist at the 
beginning of week 4 (the week of the 3rd leukapheresis/sipuleucel-T 
infusion).   
 
Patients who are not randomized (ineligible or refuses) will be deemed 
unevaluable, removed from study and followed per standard of care, 
independent of this study.   
 
Patients/research staff will not be un-blinded for the duration of the study 
except in the event of a medical emergency per section 7.5. 
 
 
5 
Treatment Plan 
In order to provide optimal patient care and to account for individual 
medical conditions, the treating physician’s discretion may be used in the 
prescribing of all supportive care drug therapy. 
5.1 
Sipuleucel-T 
Sipuleucel-T will be administered per standard of care in this study at 
either the study center or by the local referring physician.  The information 
in this section is provided for reasons of continuity and only serves as 
standard of care guidelines.   
 
5.1.1 Leukapheresis and Product Manufacturing 

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Patients will undergo leukapheresis at weeks 0, 2, and 4 with 
sipuleucel-T infused 3 days later (i.e. Monday/Thursday; Tuesday/ 
Friday); however the 3rd infusion must be done on a schedule that 
allows a clinic visit at the study center the following day. 
 
Leukapheresis will be performed at the American Red Cross who 
will ship the cells to the facility where sipuleucel-T is manufactured.  
The cell product will then be shipped to the clinical center for 
infusion.  Since the product is shipped from the manufacturer prior 
to completion of quality control (QC) testing, the cell product must 
not be infused until the Cell Product Disposition Form has 
been received by the clinical center and is marked 
“Approved.” 
 
If a cell product does not meet Dendreon quality specifications, the 
center will be contacted by telephone and the Cell Product 
Disposition Form indicating that the product is not approved will be 
faxed to the center.  Dendreon will provide instructions for the 
return or destruction of cell products that are not approved.  Refer 
to section 5.1.3 regarding repeat leukapheresis procedures. 
 
Note that if the leukapheresis appointment is delayed or 
rescheduled for any reason, the physical exam must also be re-
scheduled for completion within the 7 days preceding the 
leukapheresis procedure. 
 
5.1.2 Sipuleucel-T Administration 
Approximately 30 minutes prior to infusion, patients must be pre-
medicated with acetaminophen (650 mg) and diphenhydramine (50 
mg).  
 
Infusion of sipuleucel-T must begin prior to the labeled expiration 
time. Sipuleucel-T must be maintained in its refrigerated shipping 
package or stored at 2 to 8ºC until the cells are infused.  
 
Sipuleucel-T must be administered over approximately 60 minutes 
through a large bore IV line suitable for blood transfusion. DO NOT 
USE A FILTER.  Start and stop times of the product infusion will be 
recorded.  
 
Common treatment-emergent AEs such as pyrexia and/or rigors 
may warrant reduction of the infusion rate. If such adverse 
reactions occur, subsequent infusions should be administered over 
the shortest period that is well tolerated, but not less than 60 
minutes.  Patients must be observed for at least 30 minutes after 
the infusion.  

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5.1.3 Sipuleucel-T Product Release Failure 
In the event that a patient’s leukapheresis procedure fails or the cell 
product does not meet quality specifications, the patient may 
undergo a repeat leukapheresis procedure. There is a small 
possibility that a patient's cell product will fail to meet quality 
requirements more than once. In such instances, the patient may 
not receive all 3 infusions.  
 
In rare instances, it may be determined that it is not possible to 
make the investigational product from a patient's leukapheresis 
product that will pass the quality specifications, and he will not be 
able to receive any infusions of sipuleucel-T after multiple failed 
attempts.  
 
Patients receiving fewer than 3 doses of sipuleucel-T will not 
continue on study and receive indoximod/placebo. 
5.2 
Indoximod/Placebo 
The day after the 3rd and final sipuleucel-T infusion, the patient will begin 
indoximod 2400 mg/day or an identical appearing placebo.  The study 
drug will be continued twice daily, approximately 12 hours apart for 6 
months.  The capsules should be taken with water on an empty stomach 
one hour before breakfast and one hour before dinner.  Antacids are to be 
avoided.   
 
The patient will be provided with a daily medication log to record times of 
administration, side effects, and missed doses, if any, through week 14 
(immune monitoring endpoint).  After week 14, the patient will be asked to 
record only events such as missed doses or side effects, rather than 
keeping a daily medication log.   
 
The patient will be instructed to bring the medication log and study drug 
bottles (including any empties) to each appointment for reconcilement.   
 
5.2.1 Expected Side Effects  
All of the subjects in the indoximod clinical trials had at least one 
adverse event.  The most frequently reported adverse events 
(regardless of attribution), occurring in ≥ 20% of patients were 
fatigue, nausea, headache, and alopecia. The most frequently 
reported laboratory abnormalities (regardless of attribution), 
occurring in ≥ 20% of patients were lymphopenia, anemia and 
hyperglycemia.  
The most frequently observed adverse event which is possibly 
related to indoximod is fatigue (12%).  Lymphopenia (16%) is the 
most frequently observed laboratory abnormality possibly related to 

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indoximod.  The collective safety data from the clinical studies so 
far indicates indoximod has an acceptable safety profile and is safe 
for the treatment of patients with solid tumors.   
 
Toxicities as updated with version 6 of the indoximod investigator’s 
brochure (February 2015) are as follows: 
 
Likely:  Likely to happen to 20% or more of patients 
• Fatigue or feeling tired 
• Nausea 
• Anorexia or loss or appetite 
• Decrease in red blood cells (anemia) 
• Diarrhea 
  
Less Likely: Likely to happen to 10 to 19% of patients 
• Decrease in white blood cells (neutrophils and lymphocytes) 
• Abdominal pain  
• Feeling short of breath or breathless (dyspnea) 
• Rash 
• Vomiting 
• Constipation 
• Decrease in platelets 
• Headache 
• Hair loss 
 
Rare: Likely to happen to 1% than 10% of patients 
• Dizziness 
• Fever associated with low white blood cells 
• Lung infection 
• Increase in blood potassium, glucose, and creatinine levels  
• Sleeplessness (insomnia) 
• Low blood levels of sodium 
• Multi-organ failure 
• Low blood pressure 
• Dehydration 
• Ringing in ears 
• 
Fever associated with low white blood cells (febrile 
neutropenia) 
• 
Mouth Sores (Oral mucositis) 
• 
Decrease in white blood cells 
 
 
This drug is being employed in human clinical trials for solid tumors, 
breast cancer, melanoma, and pancreatic cancer. The profile of 
adverse events appears similar to that predicted for the study 

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subjects enrolled in these studies, e.g., a patient population with 
life-threatening disease. (7).    
 
The data obtained from the Phase 1 studies performed under 
IND78060 suggest that certain patients with a history of exposure 
to targeted biologics involving components of the IDO pathway may 
be adversely impacted following administration of indoximod. 
However, these same patients were observed to have a clinical 
response after management of the toxicity. Therefore, the 
combination of indoximod with biologic agents including ipilimumab 
is being carefully evaluated in the clinical trial setting as described 
above. 
 
The drug has not shown evidence of significant drug interactions. It 
is now being systematically tested in combination with docetaxel for 
metastatic breast cancer, in combination with ipilimumab for 
metastatic melanoma, in combination with temozolomide for 
glioblastoma, and in combination with gemcitabine/nabpaclitaxel for 
metastatic pancreas cancer in clinical trials under IND78189 and 
IND120813. 
 
Based on phase I testing no serious toxicity is anticipated. 
Therefore, no specific supportive care measures are expected to be 
required for the drug administration itself; however dose withholding 
will occur for Grade 3 and 4 treatment related toxicity per section 
5.2.3.  Unexpected adverse events will be treated as medically 
indicated by the involved physicians.   
 
Specific attention to development of autoimmune events or 
activation of latent infections will be given as trials using other 
immune-modulatory agents such as CTLA-4 blocking antibodies 
have shown a correlation between disease responses and so called 
autoimmune breakthrough events (ABEs) like hypophysitis, colitis, 
autoimmune hepatitis, or dermatitis. It is for this reason that they 
are distinguished from other adverse events.  When used 
immediately post sipuleucel-T as in this clinical trial, it might 
increase the side effects of cytokine release from last infusion of 
sipuleucel-T.  Refer to section 6.2 for study specific monitoring.  
Section 5.2.2 provides management of selected events.  
 
Placebo 
Placebo is a look-alike capsule containing no active ingredients and 
therefore no serious side effects are expected.   
 
5.2.2 Management of Selected Events During Indoximod/Placebo 
 

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Autoimmune Events 
Patients will be evaluated for autoimmune events by a checklist 
provided in Appendix IV every 2 to 8 weeks according to the 
schedule in section 6.2. This checklist, in addition to serologic tests, 
will be used by the study physicians to determine if further 
evaluation for autoimmune disease is warranted by an appropriate 
specialist in the organ system affected. This will be done to avoid 
misinterpretation of spurious autoimmune test results.   
 
Treatment with indoximod can be withheld for up to four weeks 
while the appropriate workup/supportive care is performed and a 
determination made by the primary investigator whether the patient 
can remain on trial or should discontinue treatment.  
 
Resuming treatment with indoximod after the autoimmune event 
has resolved or is stable in a patient who demonstrated an 
objective disease response may be entertained on a case by case 
basis if the principal investigator (Dr. Gupta), the treating 
investigator, and the patient agree to do so.  
 
Toxoplasma Serology  
There is some data supporting the role of Indoleamine 2,3-
dioxygenase (IDO) in the suppression of latent chronic infections.  
New headaches, mental status changes, neurological deficits, or 
visual changes should be evaluated immediately for possible CNS 
or ocular toxoplasmosis reactivation and evaluated/treated as 
needed.   
 
All patients will be screened at study entry for toxoplasma. 
 
Toxoplasma serology positive patients who do not have a sulfa 
allergy will be offered prophylaxis with Septra DS one tablet daily 
on Monday, Wednesday, and Friday.  Toxoplasma serology 
positive patients with a sulfa allergy who still want to enroll will be 
allowed to use atovaquone 750 mg twice daily administered with 
meals.  Patients who cannot tolerate or choose not to take 
prophylaxis will not be excluded from the study, but they should do 
so only after clear informed consent has been obtained about the 
possible risks of toxoplasma reactivation.   
 
Toxoplasma serology negative patients should be counseled on 
avoiding exposure to toxoplasma by avoiding direct skin contact 
with soil, cat feces, and raw meats.  Domestic cats should be kept 
indoors and be fed pet food to prevent ingestion of contaminated 
soil or meat.  Patients should thoroughly wash their hands after 
encountering any of these sources prior to eating or food 

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CPRC #2011LS109 
preparation.  All utensils and surfaces that come into contact with 
raw meats should not touch cooked or prepared food without being 
washed first.  Produce should be washed well prior to eating. Meats 
should be cooked completely until they are not pink and their juices 
run clear.  
 
Toxoplasmosis IgM and IgG titers will be checked at baseline and 
rechecked at the final treatment visit for serology negative patients.  
In addition, IgM anti toxoplasma titers will be checked if acute 
infection in serology negative patients is suspected while on study. 
 
Proteinuria 
Urine analysis will be performed every 2 weeks for 6 weeks then 
every 4 to 8 weeks thereafter. Any protein ≥ 2+ on dipstick or new 
urine active sediment/ eosinophils should be evaluated. 
 
Positive ANA Panel or Symptoms of an Autoimmune Condition 
ANA will be drawn every four weeks. Any positive panel (> 5 times 
the upper limit of normal) should reflex over to a titer panel to 
determine the specific type. Any antibody titer > 5 times the ULN 
with symptoms consistent with an autoimmune condition should 
prompt withholding of indoximod and a rheumatologic evaluation. 
Also if inflammatory arthritis develops CCP and RF antibody titers 
will be evaluated. 
 
TSH > 5 
TSH will be monitored every 4 to 8 weeks and if it increases above 
a TSH of 5 a workup for autoimmune thyroiditis will be performed 
(anti-TG and anti-TPO Ab tests, thyroid uptake scan, FNA of the 
thyroid if warranted).  
 
Also baseline and every 4 to 8 weeks, LH, FSH, ACTH, cortisol will 
be used to monitor for hypophysitis. These labs should be drawn 
between 7-8 AM due to the natural circadian variation of ACTH and 
cortisol.  If any of these tests are lower than the reference lab 
values at the clinical institution and the primary investigator 
suspects hypopituitarism then study treatment should be held and a 
workup performed.  This includes an MRI of the brain with attention 
to the sellar area to evaluate for hypophysitis. 
 
Ophthalmologic Complaints 
Any 
ophthalmologic 
complaints 
(including 
new 
ocular 
pain/inflammation, photosensitivity, or diminished vision) will be 
evaluated by an ophthalmologist if the treating investigator deems it 
necessary. 
 

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CPRC #2011LS109 
Symptoms of Myositis 
CPK will be checked if any symptoms of myositis occur. 
 
5.2.3 Indoximod /Placebo Dose Modifications (toxicity related) 
Should a patient experience a Grade 3 toxicity that is possibly, 
probably, or definitely related to the study drug as determined by 
the treating investigator, the study drug will be held.   
 
• If the toxicity resolves to Grade 2 or less within 7 days, the 
study drug may be resumed.  If the toxicity recurs the event 
will count toward the early study stopping rule for excessive 
toxicity (section 12.2).   
 
• If the toxicity does not improve to a grade 2 or less within 7 
days or recurs, the patient will be permanently discontinued 
from treatment and the event will count toward the early 
study stopping rule for excessive toxicity (section 12.2).  
 
If the patient experiences any Grade 4 toxicity, the study drug will 
be stopped and the event will count toward the early study stopping 
rule for excessive toxicity (section 12.2).  If all toxicities resolved to 
Grade 2 or less, resumption of the study drug may be considered 
but must be discussed and agreed to by the investigator and 
Principal Investigator (Dr. Gupta). 
 
5.2.4 Dosing Delays/Missed Doses (non-toxicity related) 
If a dose is delayed or missed for reasons unrelated to toxicity 
issues (i.e. patient forgets, social or employment issues, holidays, 
unrelated inter-current illness), the patient will be instructed to take 
the dose as soon as possible.  If more than 6 hours from the 
planned dosing time has passed, the dose will be skipped.  The 
patient will resume his usual dosing schedule with the next dose.  
Patients must report missed doses on the provided dose tracking 
sheet.   
5.3 
Supportive Care  
Optimal supportive care will be provided for all participants. 
5.4 
Duration of Indoximod/Placebo 
Indoximod/placebo will continue twice daily for 24 weeks unless any one 
of the following occurs: 
• Treatment related toxicity results in a discontinuation of indoximod 
/placebo for more than 7 days or a toxicity recurs despite delay  
• indoximod/placebo is discontinued for more than 4 weeks for any 
reason 
• The patient is non-compliant or withdraws consent 

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September 30, 2015  
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CPRC #2011LS109 
• Disease progression occurs, although the intent is to treat all 
patients for a minimum of 12 weeks with indoximod/placebo before 
declaring progression.  In addition, treatment will not be 
discontinued solely based on early PSA progression in the absence 
of clinical or definite radiologic progression. 
• Inter-current illness interferes with study drug administration 
• Unacceptable adverse events 
• The treating investigator or Principal Investigator feels the patient’s 
continuing participation is not in the best interest of the patient 
5.5 
Duration of Study Participation 
Patients who begin indoximod/placebo will be followed for disease 
response until progression and then survival only for 2 years from study 
enrollment. 
 
 
6 
Clinical Evaluations and Procedures  
Scheduled evaluations may be performed +/-3 days from the targeted date to 
allow for holidays and other scheduling conflicts.  The final post treatment visit 
may be performed +/- 2 weeks.  Follow-up visits may be performed +/- 4 weeks. 
In addition, targeted days may be altered as clinically appropriate. 
 
 

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6.1 Baseline and Post Treatment  
 
Study  
baseline 
Weeks 0-28 
Post rx visit 
F/U 
Evaluation 
Prior to 1st 
leukapheresis 
 
Refer to 
table in 6.2 
4 weeks 
after last 
dose of 
indoximod 
/placebo  
Every 3 
months from 
post-rx visit 
until 2 years 
from 
enrollment8 
Consent 
X 
 
 
Medical history 
X 
 
 
Physical exam 
X 
 
 
Assessment of symptoms and 
analgesic needs 
X 
X 
X 
Weight 
X 
X 
 
Vital signs 
X 
X 
 
ECOG PS 
X 
X 
 
CBC/diff/plt, CD4 count 
X 
X 
 
Bun/creatinine, Na, K, Ca, Mg, tot. 
bili, AST, ALT, alkaline phosphatase, 
LDH, albumin, total protein  
X 
X 
 
Circulating Tumor Cells (CTCs) 
X 
 
 
PT/INR, CPK 
X 
 
 
Urinalysis1 
X 
 
 
Testosterone 
X 
X 
 
HIV 1 & 2, hepatitis B, Hepatitis C, 
HTLV-1 
X 
 
 
β-HCG 
X 
 
 
ESR 
X 
 
 
EKG 
X 
 
 
CT of chest, abd, pelvis 
X 
 
X 
Bone scan  
X 
 
X 
PSA 
X 
 
X 
Research Related 
FACT-P questionnaire 
X 
 
X 
 
TSH, Free T4, LH, FSH, ACTH, 
Cortisol4 
X 
 
 
 
Toxoplasma Ab titer 
X 
X5 
 
Rheumatoid Factor 
X 
 
 
C-Reactive Protein 
X 
 
 
ANA panel3 and auto-immune 
symptom checklist (app  IV) 
X 
 
 
C3, C4, CH50 
X 
 
 
Samples for immune monitoring, K/T 
ratio and indoximod level (9 – 10 ml 
green tops, 1-10 ml red top) 
X, X6 
 
 
immune response biomarker  (1-10 
ml red top) 
X 
 
 
Optional bx7  
X 
 
 
1- 
Proteinuria – any protein ≥ 2+ on dipstick or new urine active sediment/EOS should be evaluated per 
section 5.2.2 
2- 
Toxoplasma serology positive patients will be offered prophylaxis with Septra DS per section 5.2.2 
3- 
Refer to section 5.2.2 for positive ANA panel or symptoms of an autoimmune condition 
4- 
Refer to section 5.2.2 for TSH > 5 or evidence of hypopituitarism  
5- 
Retest sero-negative patients per section 5.2.2 
6- 
Two separate sets of baseline samples to be done (i.e. at screening and prior to 1
st spiuleucel-T infusion) 
7- 
Biopsy for immune response biomarker only for those who provided additional consent within the treatment 
consent  
8- 
Once disease progression is confirmed follow for survival status only  

6.2 
During Treatment  
Treatment 
Week 
Standard of Care 
Research funded 
lab work to be 
performed by local 
(institutional) lab 
Research 
Related 
Samples  
indoximod
/ placebo 
count 
Leukapheresis followed 
by  sipuleucel-T infusion  
0 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
Leukapheresis followed 
by  sipuleucel-T infusion  
2 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
Leukapheresis followed 
by sipuleucel-T infusion, 
start indoximod /placebo 
day after infusion  
4 
Prior to 
indoximod 
/placebo 
Physical exam, 
FACT-P 
 
 
 
9 – 10 cc 
green,  
1 – 10 cc red 
(pre 
indoximod/ 
placebo) 
 
indoximod /placebo twice 
daily continuously for 6 
months 
5 
 
 
 
 
 
 
6 
PE, review of 
side effects  
 
CBC/diff/
plt, 
chem
1, 
U/A
2 
Thyroid function,  
C-reactive protein, 
ANA panel,  Auto-
immune symptom list 
9 – 10 cc 
green,  
1 – 10 cc red 
Reconcile 
Drug 
7 
 
 
 
 
 
 
8 
PE, review of 
side effects, 
FACT-P  
PSA 
CBC/diff/
plt, 
chem
1, 
U/A
2 
Thyroid function,  
C-reactive protein, 
ANA panel, Auto-
immune symptom list 
 
Reconcile 
Drug 
9 
 
 
 
 
 
 
10 
PE, review of 
side effects  
 
CBC/diff/
plt, 
chem
1, 
U/A
2 
Thyroid function,  
C-reactive protein, 
ANA panel, Auto-
immune symptom list 
9 – 10 cc 
green,  
1 – 10 cc red 
Reconcile 
Drug 
11-13 
 
 
 
 
 
 
14 
PE, review of 
side effects, 
FACT-P  
PSA, CT of 
chest, abd, 
pelvis, bone 
scan 
CBC/diff/
plt, 
chem1, 
CTCs
3, 
U/A
2 
Thyroid function,  
C-reactive protein, 
ANA panel, Auto-
immune symptom list 
9 – 10 cc 
green,  
2 – 10 cc red,  
opt biopsy 
Reconcile 
Drug 
15-19 
 
 
 
 
 
 
20 
PE, review of 
side effects, 
FACT-P  
PSA 
CBC/diff/
plt, 
chem
1, 
U/A
2 
Thyroid function,  
C-reactive protein, 
ANA panel, Auto-
immune symptom list 
 
Reconcile 
Drug 
21-23 
 
 
 
 
 
 
24 
PE, review of 
side effects  
 
CBC/diff/
plt, 
chem
1, 
protein, 
U/A
2 
 
 
 
Reconcile 
Drug 
25-27 
 
 
 
 
 
 
28 
PE, review of 
side effects, 
FACT-P 
PSA, CT of chest,
abd, pelvis, bone 
scan,  
CBC/diff/
plt, 
chem
1, 
U/A
2 
Thyroid function,  
C-reactive protein, 
ANA panel, Auto-
immune symptom list 
9 – 10 cc 
green, 1 – 10 
cc red 
Final 
Reconcile 
Drug  
 
 
1- chem to include Bun/creatinine, Na, K, Ca, Mg, tot. bili, AST, ALT, alkaline phosphatase, LDH, albumin, total protein 
2- Proteinuria – any protein ≥ 2+ on dipstick or new urine active sediment/EOS should be evaluated per section 5.2.2 
3- CTCs - circulating tumor cells

6.2.1 Immune Monitoring Studies 
At each time point in the previous table nine 10 cc green top tubes 
and one 10 cc red top tube will be collected.  An additional serum 
sample (one 10 cc red top tube) will be collected at week 14.   
 
All blood samples will be sent to Translational Therapy Laboratory 
(TTL) at University of Minnesota.  Refer to the affiliate lab manual 
for the specimen specific shipping instructions.  
 
T, NK, Treg by immunophenotype, NK cell function [CD107a and 
IFN production] measurements will be done in peripheral blood and 
tumor tissue at the Translational Therapy Laboratory (TTL) at 
University of Minnesota. 
 
ELISPOT to PA2024, ELISA to measure antibody to PA2024 will be 
done at above specified time points from the peripheral blood by 
Dendreon.  
 
Serum kynurenine, tryptophan, K/T ratio, and indoximod levels will 
be measured from peripheral blood at the specified time points by 
Newlink. 
 
The pre and week 14 serum sample will be analyzed for immune 
biomarkers by Newlink. 
 
If the patient consents at time of enrollment, aliquots of leftover 
serum will be stored from each blood draw at -80 degrees C in the 
Masonic Cancer Center’s TTL for future testing.  Permission to 
store leftover samples will be embedded in the treatment consent. 
 
 
6.2.2 Optional Biopsies 
Patients with an intact prostate or a metastatic site that can be 
easily biopsied will be invited to participate in this optional 
component of the research at the time of consent. 
 
Biopsy solely for research would be done prior to first leukapheresis 
and at 14 weeks from the first infusion of sipuleucel-T.  Patients 
with an intact prostate that has not received prior radiation will be 
preferred over a metastatic site.  
 
The core biopsy will be assessed for expression of Treg, T cells 
(CD4+ /CD8+), and NK markers.  Part of the formalin-fixed paraffin 
embedded tumor tissue will be sent by the University of Minnesota 
to the laboratory of Dr. David Munn for IDO expression by 
immunohistochemistry (IHC).  

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September 30, 2015  
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CPRC #2011LS109 
Refer to the affiliate lab manual for the specimen specific shipping 
instructions to the University of Minnesota BioNet.  
 
 
7 
Study Drug (Indoximod/Placebo) Information 
In this section, study drug is used as a general term referring to both 
indoximod and the identical looking placebo.   
7.1 
How Supplied 
Indoximod is sterile tan powder compounded in capsule form of 200 mg. 
The capsules are packaged 175 capsules per bottle in white opaque 
HDPE bottles.  The placebo consists of 313 mg of Microcrystalline 
Cellulose, NF in the identical #0el capsule used for indoximod capsules.   
 
7.2 
Manufacture and Control  
Indoximod is manufactured according to current Good Manufacturing 
Practice guidelines and NewLink Genetics Corporation specifications by a 
contracted manufacturing facility. Indoximod is tested against established 
quality specifications by the contractor and released for clinical use by 
NewLink 
Genetics 
Corporation 
Quality 
Assurance. 
 
Indoximod 
components intended for use in the clinic are placed on stability testing 
according to International Conference on Harmonization (ICH) guidelines 
to ensure that it meets specifications during the course of the clinical trial. 
 
The placebo product is manufactured according to current Good 
Manufacturing Practice guidelines and NewLink Genetics Corporation 
specifications by a contracted manufacturing facility.  The placebo 
products are tested against established quality specifications by the 
contractor and released for clinical use by NewLink Genetics Corporation 
Quality Assurance. Placebo components intended for use in the clinic are 
placed on concomitant stability testing according to International 
Conference on Harmonization (ICH) guidelines to ensure that it meets 
specifications during the course of the clinical trial. 
7.3 
Drug Procurement 
Indoximod (drug product) and placebo is shipped directly to the clinical 
sites at the direction of NewLink Genetics Corporation. Storage and audit 
of all Quality Control and Quality Assurance documentation will be 
performed by NewLink Genetics or designee. Indoximod/placebo is 
shipped by a carrier to the clinical site at room temperature. Each 
shipment is accompanied by a Drug Shipment Receipt Form. 

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7.4 
Drug Accountability 
As required by FDA regulations, all drug storage, procurement and usage 
will be carefully monitored and documented. The Principal Investigator 
and Sponsor will oversee this process and delegate responsibility as 
needed. A careful inventory will be maintained at NewLink Genetics 
Corporation and at the clinical sites. 
 
7.4.1  Drug Receipt and Inventory: 
The PI or designated individual will: 
• Complete a Drug Request Form and send to NewLink 
Genetics. NewLink will make the appropriate arrangements 
for shipment of the drug from the manufacturer. 
• Upon receipt of the investigational drug, inventory the 
shipment ensuring that the information on the packing slip 
matches exactly with what has been sent to the site, 
including the amount, lot numbers provided inventory form. 
• Promptly bring any discrepancies, breakage or evidence of 
tampering to the attention of NewLink Genetics. 
• Retain a copy of the shipping inventory, packing slips, and 
documentation of inventory in the study’s records. 
 
7.4.2  Drug Storage 
The study drug must be stored in a secure environment, with 
access limited to essential and appropriate research personnel. 
The drugs should be kept locked in a cabinet in a locked/secure 
area. The study drugs should be stored at controlled room 
temperature (within the range of 18º –25º C or 64º – 75º F) and a 
storage area daily temperature log should be maintained and 
available for monitoring at all times. Shelf-life surveillance of the 
intact bottles is on-going. 
 
7.4.3  Drug Labeling 
The study drug bottles are pre-labeled and the labels should not be 
defaced or changed in any way without written permission of 
NewLink Genetics. It is recommended that an additional label be 
placed to include the subject initials, subject study number, date 
dispensed, name of institution, study staff contact name and phone 
number. NewLink will provide these labels for the clinical site. 
 
7.4.4 Drug Dispensing  
Study drugs will be dispensed only by those who are authorized by 
the IRB approved protocol, principal investigator, state and federal 
regulations, and NewLink Genetics. 
 
Study drugs will be dispensed according to the dose, route, and 
frequency written in the clinical protocol. The PI shall dispense or 

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administer the study drug only to subjects under his/her personal 
supervision or under the supervision of a co-investigator. The 
investigator shall not dispense or supply the study drug to any 
person not authorized to receive it.  
 
A study medication binder will be created to include specific 
dispensing instructions, drug accountability form, record of drug 
dispensing, drug shipment form, and drug return form and labels.  
 
Study drug will be properly accounted for and tracked with 
adequate documentation (study medication diary). Each time the 
study drug is dispensed; there should be documentation as to the 
amount dispensed, to whom it is dispensed, and the date and 
signature or initials of the person dispensing the drug.  
 
Subjects will be instructed in the proper storage, use and 
precautions, and potential known risks of the study drug. Subjects 
should be advised to return all used and unused containers/units to 
the site of original dispensing. Study personnel should record the 
amount (number of bottles and pills, etc.) and date of return. 
Attempts to retrieve the containers/units from subjects who have 
not returned them should be documented. Any discrepancies 
between the amounts used by subjects (actual or suspected) and 
the amount returned should be documented, as well as the reasons 
for the discrepancies. 
7.5 
Breaking the Blind 
The blind shall be maintained throughout the conduct of the trial 
unless it is felt necessary to break the blind in a specific case in the 
interest of patient safety. In general, the blind will be broken after all 
the data are recorded, locked, and analyzed. The study statistician 
(Dr. Koopmeiners) will provide each site’s investigational pharmacy 
with the treatment code key. Any request to break a blind will be 
discussed with the sponsor/investigator (Dr. Gupta) and NewLink. 
7.6 
Return/Destruction of Study Drug 
At the conclusion of the study ensure that all documentation 
regarding receipt, storage, dispensing, return of used containers, 
and accountability is complete and accurate. Unused drug obtained 
from NewLink Genetics must be returned to NewLink or be 
destroyed on site using appropriate procedures upon written 
authorization from NewLink to do so. 
 
 
 

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8 
Adverse Event Documentation and Reporting 
Toxicity and adverse events will be classified according to NCI's Common 
Terminology Criteria for Adverse Events V 4.0 (CTCAE) and reported on the 
schedule below.  A copy of the CTCAE can be downloaded from the CTEP home 
page 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_
40).   
8.1 
Definitions 
The following definitions are based on the Code of Federal Regulations 
Title 21 Part 312.32 (21CFR312.32(a)). 
  
 
Adverse Event:  Any untoward medical occurrence associated with the 
use of a drug in humans, whether or not considered drug related.  
 
Suspected Adverse Reaction:  Any adverse event for which there is a 
reasonable possibility that the drug caused the adverse event.  
 
Life-Threatening Adverse Event Or Life-Threatening Suspected 
Adverse Reaction: An adverse event or suspected adverse reaction is 
considered “life-threatening” if, in the view of either the investigator or 
sponsor, its occurrence places the patient or subject at immediate risk of 
death. 
   
Serious Adverse Event Or Serious Suspected Adverse Reaction:  An 
adverse event or suspected adverse reaction is considered “serious” if, in 
the view of either the investigator or sponsor, it results in any of the 
following outcomes:  
• Death 
• A life-threatening adverse event 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions 
• A congenital anomaly/birth defect.  
 
Important medical events that may not result in death, be life-threatening, 
or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject 
and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  
 
If either the IND sponsor or the investigator believes the event is life-
threatening or serious, the event must be evaluated by the sponsor for 
expedited reporting (21CRF 312.32(a)).  
 

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Unexpected adverse event or unexpected suspected adverse 
reaction: An adverse event or suspected adverse reaction is considered 
“unexpected” if it is not listed in the investigator brochure or is not listed at 
the specificity or severity that has been observed; or, if an investigator 
brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in 
the current application, as amended.  Thus, adverse events that occur as 
part of the disease process or underlying medical conditions are 
considered unexpected; however, they will not be reportable per 8.3. 
8.2 
Adverse Event Documentation 
Monitoring for adverse events will begin with the signing of the consent 
and continue through the final treatment visit approximately 30 days after 
the last dose of indoximod/placebo.   
 
For the purposes of this study, adverse event documentation requirements 
will be determined based on grade, expectedness and relationship to 
study therapy as follows: 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 and 5 
Expected or 
Unexpected 
Expected 
Unexpected 
Expected 
Unexpected 
Expected or 
Unexpected 
Unrelated 
Unlikely 
Not required 
Not 
required 
Not required 
Not 
required 
Required 
Required 
Possible 
Probable 
Definite 
Not required 
Not 
required 
Required 
Required* 
Required* 
Required* 
 
*any grade 3 treatment related event that does not resolve to a grade 2 or 
better within 7 days and any grade 4 and 5 events will be considered 
excess and count toward an early termination event per section 12.2.  
Such events must be reported on the early study stopping event form 
found in OnCore. 
 
In addition, although not always a reportable event, deaths (date and 
cause) will be recorded in OnCore upon knowledge in the follow-up tab. 
8.3 
Required Reporting:  Affiliates to the Masonic Cancer Center 
Beginning with the signing of the consent and continuing through the final 
treatment visit, affiliate institutions will report all events meeting the 
definition of serious, regardless of attribution or expectedness, within 24 
hours of knowledge of the event to the University of Minnesota Study 
Coordinator.  After the final treatment visit, the investigator is obligated, 
upon knowledge of, to report any event that meets the definition of serious 
or life-threatening and is felt to be at least possibly related to the study 
drugs. 
 

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Reports are to be submitted to the Study Coordinator at the University of 
Minnesota Masonic Cancer Center (MCC) using the SAE reporting form 
found OnCore.  The MCC Study Coordinator will facilitate reporting to the 
University Of Minnesota IRB and the FDA as required. 
 
 
 
Affiliate institutions will be responsible for submitting reportable events to 
their institutional IRB and any other required local regulatory entities. 
 
 
 
8.4 
U of MN Required Reporting: FDA, IRB, MCC’s SAE 
Coordinator, NewLink and Dendreon  
The reporting period for this study is from initiation of any study treatment 
through the final treatment visit approximately 30 days after the last dose 
of indoximod/placebo; however after this point, the investigator must 
report upon knowledge any study treatment related event meeting the 
expedited reporting criteria below.  
 

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Agency 
Criteria for reporting 
Timeframe 
Form to 
Use 
Submission address/ 
fax numbers 
Copy to: 
U of MN 
IRB 
Events requiring prompt reporting 
including, but not limited to 
unanticipated death of a locally 
enrolled subject(s); new or increased 
risk; any adverse event  that require 
a change to the protocol or consent 
form or any protocol deviation that 
resulting in harm  
refer 
to http://www.research.umn.edu/irb/g
uidance/ae.html#.VC7xraI0-sh  
within 5 
business days 
of discovery 
 
Report 
Form 
irb@umn.edu 
 
MCC SAE 
Coordinator 
mcc-
saes@umn.edu 
FDA 
Unexpected and fatal or life 
threatening suspected adverse 
reaction 
As soon as 
possible but no 
later than 7 
Calendar-Day 
UMCC 
SAE  
Submit as an 
amendment to IND with 
a copy to all 
participating affiliate 
institutions, Dendreon, 
and NewLink  
 
 
 
 
 
1) Serious and unexpected 
suspected adverse reaction or 
2)  increased occurrence of serious 
suspected adverse reactions over 
that listed in the protocol or 
investigator 
brochure or 
3) findings from other sources (other 
studies, animal or in vitro testing) 
As soon as 
possible but no 
later than 15 
Calendar-Day 
 
All other events per CFR 312.33  
At time of FDA 
annual report 
Summary 
format 
Submit as an 
amendment to IND 
 
Not applicable 
Note:  Events due to the disease under treatment or an underlying medical condition will not require 
expedited reporting to the FDA for the purposes of this study 
Dendreon 
and 
NewLink 
(see details 
next page) 
All SAEs that occur from the signing 
of the Study-specific consent 
through the duration of the post-
therapy adverse event collection 
period (final treatment visit) 
24 hours of 
awareness of 
event 
UMCC 
SAE 
Dendreon Corporation 
Attn:  Safety Manager  
Facsimile:   (206) 829-
1647 
Phone:   (206) 219-
7899 
After Hours:  (206) 274-
6774 
 
NewLink Genetics 
Attn:  Safety Manager  
Facsimile:   (515) 296-
3556 
Phone:   (515) 598-
5020 ext 2876 
After Hours:  (515) 720-
6296 
Email:  SAE_Reporting
@linkp.com 
with a copy to all 
participating affiliate 
institutions 
 
SAE 
Coordinator 
mcc-
saes@umn.edu 

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In each IND safety report, the sponsor must identify all IND safety reports 
previously submitted to the FDA concerning a similar suspected adverse reaction 
and must analyze the significance of the suspected adverse reaction in light of 
the previous, similar reports. 
 
The SAE Coordinator will provide the Masonic Cancer Center’s Data and Safety 
Monitoring Council (DSMC) with the SAE in an appropriate format depending on 
the individual SAE (as reported or in a summary format). 
 
 
Dendreon and NewLink Serious Event Reporting 
Sponsor shall notify institution, investigator and IRB immediately during the 
conduct of the study and/or after the study is completed should it become aware 
of information related to the study that would impact participant safety or clinical 
care. Institution shall promptly disclose such information to study participants. 
 
Significant new information regarding an ongoing SAE and the resolution must 
be sent to Dendreon and NewLinks within 3 business days of awareness of the 
new information. 
 
 
9 Measurement of Effect 
9.1 Immune Response to PA2024 
The frequency of antigen specific, cytokine producing cells will be 
determined by an ELISPOT assay. ELISPOT assay will use whole PBMC 
to assess interferon gamma production in response to the immunizing 
protein PA2024. Increase in number of ELISPOT responses to PBMC in 
patients in the treatment arm will be compared to those in control arm.  
9.2  Progression Free Survival 
Progression free survival (PFS) is a composite endpoint defined as 
disease progression in bone or soft tissues, PSA progression, worsening 
pain, or death.  PFS will be measured in months from the time of study 
enrollment until the date disease progression.  During the first 12 weeks 
PSA progression alone will not be used as the sole criterion for clinical 
decision 
making 
to 
determine 
disease 
progression 
as 
per 
recommendations from Prostate Cancer Working Group -2 (PCWG2)(10).  
Masonic 
Cancer 
Center SAE 
Coordinator 
Early stopping rule event per section 
12.2 
Upon reporting 
Early 
stopping 
rule form 
SAE Coordinator 
mcc-saes@umn.edu 
Not applicable 

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9.3 
PSA Progression 
PSA 
measurements 
obtained 
during 
the 
first 
12 
weeks 
of 
indoximod/placebo will not be used as the sole criterion for establishing 
disease progression. Treatment will be discontinued if rapid disease 
progression is documented or the patient develops worsening symptoms 
of disease or toxicity. PSA progression is defined as the first PSA value 
that shows ≥ 25% increase from baseline and has a minimum absolute 
increase of ≥ 2 ng/mL after 12 weeks of treatment. 
9.4 
Imaging Progression  
Progression based on CT scans, MRI or bone scan will be defined based 
on location/type of lesion present as defined below.   
• Soft-tissue lesions – Progression will be determined by RECIST 
criteria (appendix III). 
• Bone lesions – the appearance of ≥ 2 new lesions, with the 
additional requirement that progression at first assessment be 
confirmed by a second scan 6 or more weeks later.  The 
confirmatory scan must document a minimum of 2 or more 
additional new lesions.  The date of progression is the date of the 
first scan that shows the change. 
 
 
10 
Study Data Collection and Monitoring 
10.1 Data Management 
This study will report clinical data using The Online Enterprise Research 
Management Environment (OnCoreTM), a web based Oracle® database 
utilizing study specific electronic case report forms.  Key study personnel 
are trained on the use of OnCore and will comply with protocol specific 
instructions embedded within the OnCore.  Patient demographics, patient 
specific study treatment calendars, adverse events and other information 
required for IND annual reporting will be placed in OnCore. 
10.2 Case Report Forms 
Participant data will be collected using protocol specific electronic case 
report forms (e-CRFs) developed within OnCore based on its library of 
standardized forms.  The e-CRF will be approved by the study’s Principal 
Investigator and the Biostatistician prior to release for use.  The Study 
Coordinator or designee will be responsible for registering the patient into 
OnCore at time of study entry, completing e-CRFs based on the patient 
specific calendar, and updating the patient record until the end of required 
study participation.   

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10.3 Data and Safety Monitoring Plan (DSMP) 
The study’s Data and Safety Monitoring Plan will be in compliance with the 
University of Minnesota Masonic Cancer Center's Data & Safety 
Monitoring 
Plan 
(DSMP), 
which 
can 
be 
accessed 
at http://www.cancer.umn.edu/prod/groups/ahc/@pub/@ahc/@mcc/documents/cont
ent/ahc_content_487799.pdf  
 
Monitoring For the purposes of data and safety monitoring, this study is 
classified as high risk (under a locally held IND).  Therefore the following 
requirements will be fulfilled: 
 
 The PI (Dr. Gupta) will complete and submit a quarterly Trial Progress 
Report to the Masonic Cancer Center Data and Safety Monitoring 
Council (DSMC) with the understanding the Cancer Protocol Review 
Committee (CPRC) may require more frequent reporting. 
 The PI will comply with at least twice yearly monitoring of the project by 
the Masonic Cancer Center monitoring services or designee. 
 The PI will oversee the submission of all reportable adverse events per 
the definition of reportable in section 8.4.  
 The PI will transfer affiliate site monitoring to NewLink and/or their 
designee who will, at a minimum, adhere to the University of 
Minnesota Masonic Cancer Center’s DSMP. 
 
In addition, at the time of the continuing review with the University of 
Minnesota IRB, a copy of the report with any attachments will be 
submitted to the Cancer Protocol Review Committee (CPRC). 
 
IND Annual Reports 
In accordance with regulation 21 CFR § 312.33, the IND sponsor (Dr. Jha) 
will submit a progress report annually.  The report will be submitted within 
60 days of the anniversary date that the IND went into effect.  Affiliate 
sites will be notified approximately 60 days prior to the anniversary date of 
the data cut-off date and the data run date to ensure OnCore is current 
and eCRF’s are complete. 
10.4 Monitoring 
The sponsor-investigator will permit study-related monitoring, audits, and 
inspections by the IRB, government regulatory bodies, and University of 
Minnesota compliance groups in addition to the monitoring requirements 
of the Cancer Center’s Data and Safety Monitoring Plan (section 10.3).   
 
The investigator will make available all study related documents (e.g. 
source documents, regulatory documents, data collection instruments, 
study data, etc.).  The investigator will ensure the capability for inspections 
of applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, 

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September 30, 2015  
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CPRC #2011LS109 
etc.) will be available for trial related monitoring, audits, or regulatory 
inspections. 
10.5 Record Retention 
Essential clinical documents will be maintained to demonstrate the validity 
of the study and the integrity of the data collected.  Master files should be 
established at the beginning of the study, maintained for the duration of 
the study and retained according to the appropriate regulations.   
 
The investigator will retain study records including source data, copies of 
case report forms, consent forms, HIPAA authorizations, and all study 
correspondence in a secured facility for at least 6 years after the study file 
is closed with the IRB and FDA.   
 
In addition, the Clinical Trials Office (CTO) will keep a master log of all 
patients participating in the study with sufficient information to allow 
retrieval of the medical records for that patient. Please contact the CTO 
before destroying any study related records. 
 
11 
Study Endpoints  
11.1 Primary Endpoint 
Augmentation of Tcell activation to PA2024 as measured by 
ELISPOT at 14 weeks from first leukapheresis 
11.2 Secondary Endpoints 
• Antibodies to PA2024 as measured by ELISA 
• Progression free survival 
• Objective response rate as defined by Prostate Cancer Working 
Group -2 (PCWG2)(6) 
• Overall survival and survival at two years 
• Safety and tolerability 
• Health related quality of life 
 
 
12 
Statistical Considerations 
Our primary analysis will compare Tcell activation to PA2024 as measured 
by ELISPOT at 14 weeks between treatment groups using the two-sample 
t-test for unequal variance. This analysis will be completed on log-
transformed data in the event that Tcell activation is skewed. A secondary 
analysis will be completed adjusting for any potential confounders or 
baseline differences using linear regression.(11) 
 

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Secondary endpoints CD54 count, antibodies to PA2024 and Tcell 
proliferation will be compared between groups in an unadjusted analysis 
using the two-sample t-test and an adjusted analysis using linear 
regression. Response rate will be summarized by group using contingency 
tables and the odds ratio for response will be estimated using logistic 
regression. Time to disease progression and overall survival will be 
summarized by Kaplan-Meier Curves and the hazard ratio estimated using 
Cox regression.  In addition, quality of life will be measured by the FACT-P 
(a validated questionnaire consisting of four subscales of well-being: 
Physical, Social/Family, Emotional and Functional) and compared 
between treatment groups using the two-sample t-test for univariate 
analyses and multivariate linear regression for multivariate analysis. 
12.1 
Power and Sample Size 
Previous studies showed that subjects treated with Sipuleucel-T had an 
interferon-gamma ELISPOT response to PA2024 of ~24 spots per 3 x 105 
mononuclear cells at 14 weeks with a coefficient of variation of 
approximately 1.6. Assuming that we observe a similar coefficient of 
variation and a 2.5 fold increase in the ELISPOT assay (an average of ~60 
spots per 3 x 105 mononuclear cells) in those treated with Sipuleucel-T 
plus the addition of indoximod, a total sample size of 50 (25 subjects per 
group) will provide 80% power to reject the null hypothesis at the 0.05 
level using a two-sample t-test to compare log-transformed expression 
levels between the two groups. 
12.2 
Early Termination for Excess Toxicity 
O’Brian-Fleming group sequential stopping boundaries will be used to 
monitor for excess toxicity(11). Excess toxicity will be defined as CTCAE 
v4 grade 3 treatment related events that do not resolve to a grade 2 or 
better within 7 and any grade 4 and 5 events.  We assume that a toxicity 
rate of 10% or lower is acceptable. The study will terminate for excess 
toxicity if 3 toxicities are observed in the first 5 subjects, 4 toxicities are 
observed in the first 15 subjects or 5 toxicities are observed at any point 
during the study. This stopping boundary has a type-I error rate of 0.1 (i.e. 
the probability of concluding excess toxicity when the true rate of toxicity is 
only 10%) and has 90% power to stop for excess toxicity if the true rate of 
toxicity is 30%.  
 
 

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13 
References 
1.  http://seer.cancer.gov/csr/1975_2007/results_single/sect_01_table.01.pdf (SEER 
STATFACTS accessed on 10/18/2011 
2. Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, et al. 
Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials 
of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. 
Cancer. 2009;115(16):3670-9. 
3. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. 
Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 
2010;363(5):411-22. 
4. Prendergast GC. Immune escape as a fundamental trait of cancer: focus on IDO. 
Oncogene. 2008;27(28):3889-900. 
5. Colombo MP, Piconese S. Regulatory-T-cell inhibition versus depletion: the right 
choice in cancer immunotherapy. Nat Rev Cancer. 2007;7(11):880-7. 
6.   Sarwar, G. and Botting, H.G. (1999) Liquid concentrates are lower in bioavailable 
tryptophan than powdered infant formulas, and tryptophan supplementation of 
formulas increases brain tryptophan and serotonin in rats. J. Nutr. 129; 1692-1697. 
7. 1-methyl-D-tryptophan (Investigator's Brochure). Ames, IA: NewLink Genetics; 
version 4 dated: 09/25/2012 (updated 2/16/2015 version 6) .  
8. Gurtner, G. J., Newberry, R. D., Schloemann, S. R., McDonald, K.G., and Stenson, 
W. F. (2003). Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene 
sulfonic acid colitis in mice.Gastroenterology 125; 1762-1773.  
9 
Sakurai, K., Zou, J., Tschetter, J., Ward, J., and Shearer, G. (2002).Effect of 
indoleamine 2,3-dioxygenase on induction of experimental autoimmune 
encephalomyelitis. J. Neuroimmunol. 129; 186-196. 
10. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design 
and end points of clinical trials for patients with progressive prostate cancer and 
castrate levels of testosterone: recommendations of the Prostate Cancer Clinical 
Trials Working Group. J Clin Oncol. 2008;26(7):1148-59. 
11. O’Brien, P.C. and Fleming, T.R. (1979) A multiple testing procedure for clinical trials. 
Biometrics, 35, 549-556.

Appendix I – Eligibility Checklist 
A Randomized, Double-Blind Phase II Study of Sipuleucel-T (Provenge®) and Followed 
by Indoximod or Placebo in the Treatment of Patients with Asymptomatic or Minimally 
Symptomatic Metastatic Castration Resistant Prostate Cancer  
Eligibility Checklist – page 1 of 2 
Patient initials   
    Enrolling Institution __________________________sequence #
 
 
 
 
 
 
 
 
 
 
assigned by ONCORE at enrollment  
 
INCLUSION CRITERIA  
A "NO" response to any of the following disqualifies the patient from study entry. 
 
 
Yes      No 
1-  Histologically documented adenocarcinoma of the prostate with metastatic disease as 
evidenced by soft tissue (e.g. lymphoid) and/or bony metastases on baseline CT scan 
of the abdomen and pelvis and/or bone scan 
 
 
2-  Castration-resistant based on a current or historical evidence of disease progression 
despite surgical or medical castration as demonstrated by one or more of the following: 
PSA progression defined as two consecutive PSA measurements at least 14 days 
apart ≥ 2.0 ng/ml and ≥ 50% above the minimum PSA during castration therapy or 
above pre-treatment value if no response 
progression of measurable disease based on RECIST (≥ 20% increase in the sum 
of the diameters of all target lesions or the development of any new lesions) 
progression of non-measureable disease by imaging per section 9.4 of protocol 
 
 
3-  Serum PSA ≥ 2.0 ng/ml at study enrollment PSA 
.
 ng/ml  Date
/
/
 
 
 
4-  Castration levels of testosterone defined as ≤ 50 ng/dL at study enrollment 
Testosterone level  
.
 ng/dL            Date
/
/
 
Must be at least 3 months from surgical castration or must have received medical 
castration therapy for at least 3 months and be continuing on such therapy at the time 
of confirmed disease progression 
 
 
 
5-  Asymptomatic or minimally symptomatic disease as demonstrated by ECOG 
Performance Status 0 or 1 (appendix II) and no need for opiate pain medications to 
control pain/symptoms PS 
 
 
 
6-  Age 18 years and older 
 
 
7-  Adequate organ function within 14 days of study enrollment defined as: 
Test or 
evaluation 
Required Value 
Patient’s Value 
Date of Result 
WBC or  
CD4 count 
>3,000/mcL OR  
,
 
/
/
 
>400 cells/mm3 
,
 
/
/
 
PLT 
>100,000/mcL 
,
 
/
/
 
Creatinine o
r Creatinine 
Clearance 
< 2.0 mg/dL 
Or  
> 60 mL/min/1.73 m2 
.
 
Or 
.
 
/
/
 
total bilirubin 
< 1.5 x institutional 
ULN value 
.
  
.
 
/
/
 
AST(SGOT) 
< 2.5 x institutional 
ULN   
value 
,
 
,
 
/
/
 
ALT (SGPT) 
< 2.5 x institutional 
ULN 
value 
,
 
,
 
/
/
 
 
 
8-  Voluntary written consent 
 
 

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CPRC #2011LS109 
A Randomized, Double-Blind Phase II Study of Sipuleucel-T (Provenge®) Followed 
by Indoximod or Placebo in the Treatment of Patients with Asymptomatic or 
Minimally Symptomatic Metastatic Castration Resistant Prostate Cancer 
Eligibility Checklist – page 2 of 2 
Patient initials   
    Enrolling Institution __________________________ 
 
 
EXCLUSION CRITERIA  
A "YES" response to any of the following disqualifies the patient from study entry. 
 
 
Yes      No 
9-  Visceral metastases (e.g. lung, liver, brain, kidney, spleen) as the safety and efficacy of 
sipuleucel-T has not been established in this patient population 
 
 
10- Use of systemic corticosteroids or other immunosuppressive agents within the previous 
4 weeks of study enrollment 
 
 
11- HIV-positive patients and those with other acquired/inherited immunodeficiencies 
 
 
12- Active hepatitis including hepatitis B or C 
 
 
13- History of gastrointestinal disease causing malabsorption or obstruction such as, but 
not limited to Crohn’s disease, celiac sprue, tropical sprue, bacterial overgrowth/blind 
loop syndrome, gastric bypass surgery, strictures, adhesions, achalasia, bowel 
obstruction, or extensive small bowel resection 
 
 
 
14- Inability to take medications by mouth 
 
 
15- History of allergic reactions attributed to compounds of similar chemical or biologic 
composition of those used in this study 
 
 
16- Active autoimmune disease, chronic inflammatory condition, conditions requiring 
concurrent use of any systemic immunosuppressants or steroids. Mild-intermittent 
asthma requiring only occasional beta-agonist inhaler use or mild localized eczema will 
not be excluded 
 
 
17- Previous allo-transplant of any kind 
 
 
18- History of prior treatment with anti-CTLA4 blocking antibody 
 
 
 
 
Date consent form signed: 
 
 
 
 
 
Agrees to optional biopsy component  yes 
        no  
 
 
Having obtained consent and reviewed each of the inclusion/exclusion criteria, I verify that this patient is:  
 
 
  Eligible 
  Ineligible 
   Date registered  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of person verifying eligibility 
 
 

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CPRC #2011LS109 
Appendix II - Performance Status Scales 
 
 
ECOG PERFORMANCE STATUS CRITERIA  
Grade  
Performance Criteria  
Karnofsky Scale 
equivalent  
0  
Normal activity. Fully active, able to carry on all pre-disease 
performance without restriction.  
(90-100)  
1  
Symptoms but ambulatory. Restricted in physically 
strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature (e.g., light housework, office 
work).  
(70-80)  
2  
In bed <50% of the time. Ambulatory and capable of self-
care, but unable to carry out any work activities. Up and 
about more than 50% of waking hours.  
(50-60)  
3  
In bed >50% of the time. Capable of only limited self-care, 
confined to bed or chair more than 50% of waking hours.  
(30-40)  
4  
100% bedridden. Completely disabled. Cannot carry on any 
self-care. Totally confined to bed or chair.  
(10-20)  
5  
Dead  
(0)  
 
 
 

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CPRC #2011LS109 
Appendix III – RECIST v 1.1 
Response and progression will be evaluated in this study using the international criteria proposed by the 
revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-
247, 2009].  Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the 
shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. 
 
 
Disease Parameters 
Measurable disease.  Measurable 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, as >10 mm with CT 
scan, or >10 mm with 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.  If the investigator thinks it appropriate to include them, the conditions under which such 
lesions should be considered must be defined in the protocol. 
 
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. 
 
Non-measurable disease.  All other lesions (or sites of disease), including small lesions (longest diameter 
<10 mm or pathological lymph nodes with ≥ 10 to <15 mm short axis), are considered non-measurable 
disease.  Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by CT or MRI), are 
considered as non-measurable. 
 
Note:  Cystic lesions that meet the criteria for radiographically 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 lesions, 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. 
 
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 their 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 itself 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 calculated 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.  Measurements of these lesions are not required, but the presence, absence, or in rare cases 
unequivocal progression of each should be noted throughout follow-up.  
 
 
 

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CPRC #2011LS109 
Methods for Evaluation of Measurable Disease  
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All baseline 
evaluations should be performed as closely as possible to the beginning of treatment and never more 
than 4 weeks before the beginning of the treatment. 
 
The same method of assessment and the same technique should be used to characterize each identified 
and reported lesion at baseline 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 specifications 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 
on 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 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 routinely or serially performed.   
 
 
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 least 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 

Sipuleucel-T Followed by Indoximod or Placebo in Castration Resistant Prostate Cancer 
 
 
 
 
September 30, 2015  
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CPRC #2011LS109 
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 the smallest sum diameters while on 
study. 
 
Evaluation of Non-Target Lesions 
 
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level.  All lymph nodes must be non-pathological in size (<10 mm 
short axis) 
Note:  If tumor markers are initially above the upper normal limit, they 
must normalize for a patient to be considered in complete clinical 
response. 
 
Non-CR/Non-PD: 
 
Persistence of one or more non-target lesion(s) and/or maintenance of 
tumor marker level above the normal limits 
 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression 
of existing non-target lesions.  Unequivocal progression should not 
normally trump target lesion status.  It must be representative of overall 
disease status change, not a single lesion increase.     
Although a clear progression of “non-target” lesions only is exceptional, 
the opinion of the treating physician should prevail in such 
circumstances, and the progression status should be confirmed at a later 
time by the review panel (or Principal Investigator). 
 
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 response assignment will depend on the 
achievement of both measurement and confirmation criteria. 
For Patients with Measurable Disease (i.e., Target Disease) 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation 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 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. 

Sipuleucel-T Followed by Indoximod or Placebo in Castration Resistant Prostate Cancer 
 
 
 
 
September 30, 2015  
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CPRC #2011LS109 
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. 
 
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 
 
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.  
 
Progression-Free Survival 
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first. 
 
 
 

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CPRC #2011LS109 
Appendix IV - Auto-Immune Symptom Evaluation Checklist 
 
Patient ID: __________________________    Week #:___    Date: __________ 
 
Organ System 
Present 
Absent 
SKIN: Any new rashes, itching, lesions, change in skin color, 
or hair loss? 
 
 
 
EYES: Any change in vision, blurring, haloes, floaters, 
pain/sensitivity to light, pain with eye movement, eye irritation, 
dryness, discharge, or excessive tearing? 
 
 
 
NERVOUS SYSTEM: Any new recurrent headaches, change 
in mental function, muscle weakness, or numbness? 
 
 
 
LUNGS: Any new wheezing, shortness of breath, cough? 
 
 
 
CARDIAC: Any new chest pain, palpitations, irregular heart 
beats, shortness of breath with exertion or lying flat, or 
swelling in the legs? 
 
 
 
GASTROINTESTINAL: Any new abdominal pain, 
nausea/vomiting, diarrhea, blood or pus in the stool, jaundice? 
 
 
 
GENITOURINARY: Any bloody or cloudy urine, pain with 
urination, flank pain, or new lesions/rashes the genital area? 
 
 
 
MUSCULOSKELETAL: Any new swollen, painful, and warm 
joints? Any new muscle soreness/weakness? 
 
 
 
ENDOCRINE: Do you constantly feel cold while others around 
you are not? Any coarsening of your hair, 
deepening/hoarseness of your voice, thickening of your skin in 
your face, arms, or legs? 
 
 
 
GENERAL: Any worsening fatigue or fevers? 
 
 
 
 
 
_______________________________________ __________________ 
Evaluator Signature  
 
 
 
 
Date 
 

Appendix V – FACT P (version 4) 
Patient ID: __________________________    Week #:___    Date: __________ 
 
Below is a list of statements that other people with your illness have said are important. Please circle 
or mark one number per line to indicate your response as it applies to the past 7 days. 
 
Please circle or mark one number per line to indicate your response as it applies to the past 7 
days. 
 
 
PHYSICAL WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GP1 
I have a lack of energy ........................................................
0 
1 
2 
3 
4 
GP2 
I have nausea ......................................................................
0 
1 
2 
3 
4 
GP3 
Because of my physical condition, I have trouble 
meeting the needs of my family .........................................
 
0 
 
1 
 
2 
 
3 
 
4 
GP4 
I have pain ..........................................................................
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment .........................
0 
1 
2 
3 
4 
GP6 
I feel ill ...............................................................................
0 
1 
2 
3 
4 
GP7 
I am forced to spend time in bed ........................................
0 
1 
2 
3 
4 
 
 
SOCIAL/FAMILY WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GS1 
I feel close to my friends ....................................................
0 
1 
2 
3 
4 
GS2 
I get emotional support from my family ............................
0 
1 
2 
3 
4 
GS3 
I get support from my friends .............................................
0 
1 
2 
3 
4 
GS4 
My family has accepted my illness ....................................
0 
1 
2 
3 
4 
GS5 
I am satisfied with family communication about my 
illness ..................................................................................
 
0 
 
1 
 
2 
 
3 
 
4 
GS6 
I feel close to my partner (or the person who is my main 
support) ...............................................................................
 
0 
 
1 
 
2 
 
3 
 
4 
Q1 
Regardless of your current level of sexual activity, please answer the following question. If you prefer not to 
answer it, please mark this box           and go to the next section. 
GS7 
I am satisfied with my sex life .............................................
0 
1 
2 
3 
4 

Sipuleucel-T Followed by Indoximod or Placebo in Castration Resistant Prostate Cancer 
 
 
 
 
September 30, 2015  
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CPRC #2011LS109 
 
 
 
EMOTIONAL WELL-BEING 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GE1 
I feel sad ..............................................................................
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with my illness ..........
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my illness ..................
0 
1 
2 
3 
4 
GE4 
I feel nervous .......................................................................
0 
1 
2 
3 
4 
GE5 
I worry about dying .............................................................
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get worse ............................
0 
1 
2 
3 
4 
 
 
 
 
FUNCTIONAL WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GF1 
I am able to work (include work at home) ..........................
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is fulfilling .....................
0 
1 
2 
3 
4 
GF3 
I am able to enjoy life ..........................................................
0 
1 
2 
3 
4 
GF4 
I have accepted my illness ...................................................
0 
1 
2 
3 
4 
GF5 
I am sleeping well ................................................................
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for fun ......................
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right now ..............
0 
1 
2 
3 
4 
 
 
 

Sipuleucel-T Followed by Indoximod or Placebo in Castration Resistant Prostate Cancer 
 
 
 
 
September 30, 2015  
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CPRC #2011LS109 
 
Please circle or mark one number per line to indicate your response as it applies to the past 7 
days. 
 
 
 
ADDITIONAL CONCERNS 
 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
C2 
I am losing weight ...............................................................
0 
1 
2 
3 
4 
C6 
I have a good appetite ..........................................................
0 
1 
2 
3 
4 
P1 
I have aches and pains that bother me .................................
0 
1 
2 
3 
4 
P2 
I have certain parts of my body where I experience pain ....
0 
1 
2 
3 
4 
P3 
My pain keeps me from doing things I want to do ..............
0 
1 
2 
3 
4 
P4 
I am satisfied with my present comfort level ......................
0 
1 
2 
3 
4 
P5 
I am able to feel like a man .................................................
0 
1 
2 
3 
4 
P6 
I have trouble moving my bowels .......................................
0 
1 
2 
3 
4 
P7 
I have difficulty urinating ....................................................
0 
1 
2 
3 
4 
BL2 
I urinate more frequently than usual ....................................
0 
1 
2 
3 
4 
P8 
My problems with urinating limit my activities ..................
0 
1 
2 
3 
4 
BL5 
I am able to have and maintain an erection .........................
0 
1 
2 
3 
4