Clinical trial NCT04635059
Conditions: Prostate Cancer
Sponsor: Medical College of Wisconsin
Start date: 2021-06-01; Completion date: 2024-10-27
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a single-arm, open-label study using pacritinib for patients with histologically confirmed prostate adenocarcinoma, status post definitive treatment and biochemical recurrence.

Detailed description:
This phase 2, single-arm, open-label study using pacritinib will treat patients with histologically confirmed prostate adenocarcinoma, status post definitive treatment and biochemical recurrence.

The primary objective of this study is to determine the effect of pacritinib on the time to prostate-specific antigen (PSA) progression in patients with biochemical relapse of prostate cancer (defined as the length of time that a given subject will be alive and free from PSA progression per Prostate Cancer Working Group 3 (PCWG3) guidelines.

Arms: arm 1: Pacritinib is an oral drug.
Interventions: intervention 1: Pacritinib
Intervention descriptions: intervention 1: Pacritinib is an oral drug which will be taken daily on a 28-day cycle at a dose of 200 mg twice a day (BID).

Protocol documents:
Prot_SAP_000.pdf: 
 
Oﬃcial Ɵtle:  PacriƟnib for Biochemical Relapse AŌer DeﬁniƟve Treatment for 
Prostate Cancer 
NCT04635059 
Version date 04/20/2023 


Study Short Title: IIT-Kilari-J31001-BLAST
1
Version No.: 2
IND No.: 153617
Version Date: 04/20/2023
A Single-Arm, Open-Label, Phase 2 Study Evaluating PacritiniB for 
Patients with BiochemicaL RelApse after Definitive Treatment for 
ProStaTe Cancer
Short Title:
Deepak Kilari, MD (Study PI)
Marja Nevalainen, MD (CO-PI)
Current Version Number and Date
v2.0 
04/20/2023
Proprietary and Confidential
The information in this document is considered privileged and confidential and may not 
be disclosed to others except to the extent necessary to obtain Institutional Review 
Board approval and informed consent, or as required by federal and state laws. Persons 
to whom this information is disclosed should be informed that this information is 
privileged and confidential and that it should not be further disclosed.
BLAST
Study


Study Short Title: IIT-Kilari-J31001-BLAST
2
Version No.: 2
IND No.: 153617
Version Date: 04/20/2023
Title:
A Phase 2 Study of Pacritinib for the Management of Patients with Biochemical 
Relapse after Definitive Treatment for Prostate Cancer
MCW Protocol No.: IIT-Kilari-J31001-
BLAST
IRB Pro No.: 40162
Clinical trials.gov No.: NCT04635059
FDA IND No.: 153617
Principal Investigator:
Deepak Kilari, MD
Associate Professor
Department of Medicine
Division of Hematology/Oncology
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4600
Email: dkilari@mcw.edu
Co-Principal Investigator:
Marja Nevalainen, MD
Assistant Dean and Professor of Pathology
Froedtert & Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
Telephone: 414-955-2103
Email: mnevalainen@mcw.edu
Sub-Investigator:
Kathryn Bylow, MD
Associate Professor
Department of Medicine
Division of Hematology/Oncology
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4600
Email: kbylow@mcw.edu
Sub-Investigator:
Ariel Nelson, MD
Assistant Professor
Department of Medicine
Division of Hematology/Oncology
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4600
Email:  kbylow@mcw.edu
Sub-Investigator:
William Hall, MD
Associate Professor
Department of Radiation Oncology 
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4462
Email:  whall@mcw.edu
Sub-Investigator:
Scott Johnson, MD
Assistant Professor
Department of Urology  
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-0805
Email:scjohnson@mcw.edu
Sub-Investigator:
Thomas Giever, MD                                                       
Assistant Professor
Department of Medicine
Division of Hematology/Oncology
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4600
Email:  tgiever@mcw.edu


Study Short Title: IIT-Kilari-J31001-BLAST
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IND No.: 153617
Version Date: 04/20/2023
Sub-Investigator:
John Burfeind,
MD                                                              
Associate Professor
Department of Medicine
Division of Hematology/Oncology
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4600
Email:  jburfeind@mcw.edu
Sub-Investigator:
Peter Langenstroer, MD
Professor 
Department of Urology  
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone:414-805-0805
Email: plangenstroer@mcw.edu
Sub-Investigator: 
Hallgeir Rui, MD
Professor 
Department of Pathology
8701 Watertown Plank Road
Milwaukee, WI 53226
Telephone: 414-955-2110
Email: hrui@mcw.edu
Sub-Investigator: 
Manpreet Bedi, MD                                     
Associate Professor
Department of Radiation Oncology 
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4400
Email:  mbedi@mcw.edu
Sub-Investigator: 
Colleen Lawton, MD                                   
Professor
Department of Radiation Oncology 
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4472
Email:  clawton@mcw.edu
Biostatistician:
Aniko Szabo, PhD
Associate Professor
Institute for Heath and Society
Division of Biostatistics
8701 Watertown Plank Road
Milwaukee, WI 53226
Sub-Investigator: 
Parag Tolat, MD
Associate Professor 
Department of Radiology
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-3000
Email: ptolat@mcw.edu
Sub-Investigator: 
Kenneth Jacobsohn, MD                                                
Professor
Department of Urologic Surgery
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-955-0866
Email:  kjacobsohn@mcw.edu
Sub-Investigator: 
Michael Straza, MD                                                        
Assistant Professor
Department of Radiation Oncology 
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
Telephone: 414-805-4477
Email:  mstraza@mcw.edu


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414-955-4096 
Email: aszabo@mcw.edu  
Funder: 
MCW Cancer Center 
Drug supply
CTI BioPharma


Study Short Title: IIT-Kilari-J31001-BLAST
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PROTOCOL SUMMARY
Title
A Phase 2 Study of Pacritinib for the Biochemical Relapse after 
Definitive Treatment for Prostate Cancer
IND Sponsor
Investigator-Sponsor
Principal Investigator 
Deepak Kilari, MD
Clinical Trial Phase
Phase 2
Study Population
Patients with histologically or cytologically confirmed prostate 
adenocarcinoma, status post definitive treatment and biochemical 
recurrence.
Primary Objectives
To determine the effect of pacritinib on the time to PSA progression in 
patients with biochemical relapse of prostate cancer (defined as the 
length of time that a given subject will be alive and free from PSA 
progression per PCWG3 guidelines).
Secondary Objectives
1.
To evaluate the absolute PSA nadir as a result of treatment. 
2.
To determine the time to PSA nadir from the start of treatment.
3.
To determine the time to subsequent antineoplastic therapy 
4.
To determine the effect of investigational treatment on 
testosterone levels  
5.
To determine the safety and toxicities of the study drug. 
Explorative
Objectives
1.
To determine the effect of study drug on comprehensive 
geriatric assessment domains. 
2.
To determine the effect of the study drug on short-term and 
long-term health-related quality of life (HRQOL)
3.
To evaluate if positive status for Stat5 activation in the 
paraffin-embedded tissue sections of the most recent biopsy
specimen has a trend to predict biochemical response to 
pacritinib treatment
Study Design
Single-arm, open-label study.
Study Agent
Pacritinib 200 mg BID.
Number of Subjects
N= 46. The first cohort of the study will enroll 10 patients. Enrollment to 
the second cohort(n=36) would be dependent on the response noted in 
the first cohort and funding.
Estimated Time to 
Complete Enrollment:
Approximately 12 months for the first 10 patients and 36 months for 
total study.


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Inclusion criteria 
Histologically 
or 
cytologically 
confirmed 
prostate 
adenocarcinoma.
Prior radical prostatectomy or definitive radiation therapy.
Biochemically recurrent prostate cancer with PSA doubling time 
9 months at the time of study entry. 
Prior adjuvant or salvage radiation or not a candidate for 
radiation based upon clinical assessment of disease.
characteristics and patient comorbidities.
Screening PSA > 0.5 ng/mL.
No definitive evidence of metastases on screening imaging per 
the judgment of the investigator. Pelvic lymph nodes measuring
1.5 cm or less in short axis diameter are allowed. 
Screening serum testosterone > 50 ng/dL.  
Eastern Cooperative Oncology Group (ECOG) Performance 
Status grade 0-1
70.
.
,
Agrees to use a condom (even men with vasectomies) and 
another effective method of birth control if he is having sex with 
a woman of childbearing potential.
Adequate organ function.
Left ventricular cardiac ejection fraction of
50% by 
echocardiogram or multigated acquisition scan.
Adequate coagulation defined by prothrombin time/international 
.
Exclusion criteria 
Prior systemic treatment with androgen deprivation therapy 
and/or first-generation anti-androgen (e.g. bicalutamide, 
nilutamide, flutamide) for biochemically recurrent prostate 
cancer (prior systemic treatment in the neoadjuvant, setting with 
definitive and/or salvage RT allowed as long as the interval 
between completion of systemic treatment and the start of 
pacritinib
12 months)
Prior treatment with CYP17 inhibitor (e.g., ketoconazole, 
abiraterone acetate, galeterone) or next-generation androgen 
receptor antagonist including apalutamide or enzalutamide.
Prior chemotherapy for prostate cancer 
Use of 5-alpha reductase inhibitor within 42 days before
randomization.
Use of investigational agent within 28 days before
randomization.
Use of other prohibited medications within seven days before
Cycle 1 Day 1 on study.
Prior bilateral orchiectomy.
Uncontrolled hypertension.
Gastrointestinal disorder affecting absorption or the ability to 
swallow tablets.
Baseline severe hepatic impairment (Child-Pugh Class B & C) 
Intercurrent illness that is not controlled, such as active 
infection, psychiatric illness/social situations that would limit 
compliance with study requirements.


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Any chronic medical condition requiring a higher dose of 
corticosteroid than the equivalent of 10-mg prednisone
/prednisolone per day.
Statistics 
A two-stage design based on the methods of Huang et al (2010) will be 
used. The null hypothesis that the median PSA-progression-free 
survival is six months will be tested against a one-sided alternative by 
for the six-month PSA-progression-free survival probability exceeding 
50%. The study is designed to have 80% power to obtain a result 
significant at a one-sided 10% level if the experimental treatment has a 
six-month PSA-progression-free probability of 66%, which corresponds 
to a median of 10 months if the time to PSA progression is exponentially 
distributed.
The design is based on a modification of a binomial two-stage design 
that allows the incorporation of data from subjects with less than six
months of follow-up at the interim analysis. The study will enroll up to 
46 subjects with an interim analysis performed when 10 patients have 
been treated and followed for six months. 
Pacritinib Dosage
Modifications
Pacritinib dosage may be interrupted or modified for pacritinib-related 
hematologic toxicities, hemorrhage, severe infections, cardiac toxicities 
(including QTcF interval prolongation and reduction in ejection fraction), 
diarrhea, and other pacritinib-related
nonhematologic toxicities. 
Pacritinib dosage may also be held for invasive procedures or at the
discretion of the investigator. Refer to Section 5.2 for pacritinib dosage 
management guidelines.
Safety 
Safety and tolerability will be assessed primarily by the incidence, 
severity, and change from baseline in safety parameters, such as 
treatment-emergent AEs (TEAEs; including SAEs), laboratory values, 
cardiac assessments, and vital signs.




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STUDY CALENDAR
Study Assessments
Screening1
Cycle 12
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 5 
Cycle 6 and 
beyond
(Treatment till 
progression) 
Progression +/- 714
End of 
treatment1
2 (EOT) 
visit
Follow-
up
(2 years)3
Each Cycle (28 days)
30-day 
post-last 
dose 
Safety 
Visit
(±7 days)
Every 6 
months 
post EOT 
visit 
(±21days)
Day – 30
to -1
(in Days)
Every 2
months (± 7 
days)
1
15±3
±3
±3
±3
±3
Informed consent
X
Medical History11
X
AE reporting 
Recorded from Day 1 through 30 days after the last dose of study drug.
Concomitant 
Medications
Recorded from the signing of the ICF through 30 days after the last dose of study drug.
Physical Exam
X
X
X
X
X
X
X
X
X
X
Vital Signs4
X
X
X
X
X
X
X
X
X
X
ECOG Performance 
Status 
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG5
X
X
X
X
X5
Transthoracic 
echocardiogram (TTE)6
X
X
X
X6
Comprehensive 
Geriatric Assessment
X
X
Tissue for STAT 5 
analysis 10
X
Serum PSA
X
X
X
X
X
X
X
X
X
X
Serum Testosterone
X
X
CBC w/ Diff 
X
X
X
X
X
X
X
X
X
X
Blood Chemistry8
X
X
X
X
X
X
X


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Study Assessments
Screening1
Cycle 12
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 5 
Cycle 6 and 
beyond
(Treatment till 
progression) 
Progression +/- 714
End of 
treatment1
2 (EOT) 
visit
Follow-
up
(2 years)3
Each Cycle (28 days)
30-day 
post-last 
dose 
Safety 
Visit
(±7 days)
Every 6 
months 
post EOT 
visit 
(±21days)
Day – 30
to -1
(in Days)
Every 2
months (± 7 
days)
1
15±3
±3
±3
±3
±3
Coagulation (PT/PTT) 
and Hb A1C
X
Research blood draw 
X
X
X
X
CT of Abdomen and 
Pelvis. /CT 
urogram/MRI abdomen 
and pelvis/PET 9, 13,15
X
X
X
Bone scan9, 13, 15
X
X
X
Chest Imaging9,15
X
X
Pacritinib dispense 
X7
X7
X
X
X7
X7
Patient-reported
outcome
instrument: - FACT-P
X
X
X
1.
All screening procedures must occur within 30 days prior to treatment initiation.
2.
Day 1 assessments are required to be performed prior to initiation of study treatment and can be performed up to 24 hours prior to 
initiation of study treatment. Study days are to be counted based on the start of treatment.
3.
If a subject has disease progression or subject withdrawal, then they will be followed as per follow-up requirements. Patients will be in 
follow up for 2 years from EOT visit.
4.
Vital signs include systolic and diastolic blood pressure, pulse, respiratory rate, temperature, and body weight.
5.
A 12-lead ECG (collected in triplicate), including QTcF, will be performed at Screening, and then predose at C1D1, C2D1,, C5D1, C7D1, 
and every four months (every other cycle/odd cycles) thereafter provided normal QTcF.. if QTc is prolonged, more frequent monitoring will 
be done after discussion with sponsor. For patients who have discontinued treatment, ECGs are to be performed at the End-of-Treatment 
Visit but are not otherwise required
6.
TTE will be performed at screening, C2D1, C5D1, C8D1, and every six months thereafter (every 3 cycles) provided normal LVEF and no 


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clinical evidence of heart failure. Window for all TTEs is -14 days from Day 1 of the cycle it is due for.
7.
On days when ECGs are to be obtained, Pacritinib will be administered in the clinic to facilitate the performance of pre-dose assessments
8.
Serum chemistry values will include ALT/SGPT, AST/SGOT, alkaline phosphatase, bilirubin (total, direct, and indirect) creatinine, LDH, 
sodium, potassium, chloride, bicarbonate, calcium, phosphate, magnesium, BUN/urea, albumin, glucose, cholesterol (fasting not 
required), and uric acid. Serum chemistry results obtained from unscheduled visits should be entered into the electronic database.
Additional serum chemistry testing should be done as clinically indicated.
9.
Unscheduled visits should include physical examination, laboratory tests, and radiographic evaluations as clinically indicated in the 
judgment of the investigator and these results must be entered into the clinical database (e.g., electronic data capture). Additional visits 
may be required for patients who have pacritinib dose modifications due to hematologic, cardiac, diarrhea, or other non-hematologic
toxicities. Results of clinical laboratory assessments at unscheduled visits should be entered into the electronic database.
10. Core biopsy or surgical specimens from primary prostate cancer prior to administration of Jak2 inhibitor as well as other archive tissue (if 
available) will be used for study biomarker assessments. Tissue from surgical specimen will be preferred over core biopsy specimens when 
available. One hematoxylin and eosin slide and five unstained slides from formalin-fixed, paraffin-embedded pathology blocks with cancer 
will be reserved for study labs/biomarkers. If adequate tissue is not available, the patient would still qualify and be enrolled to the study.
11. Including demographics form
12. Treatment duration is expected to be 2 years. Patients may continue drug beyond 2 years, if in the opinion of the treating physician, the 
patient is benefitting from treatment and benefits outweigh the risks of therapy. 
13. imaging due at Cycle 4 has a 14-day window
14. If any of the required progression assessments have already been completed in the last 30 days, at the treating physician’s discretion, they 
do not need to be repeated. 
15. If PSMA/Axumin PET imaging is performed at baseline, other imaging is not required in addition to PET. Different modalities may be used 
at each imaging timepoint based on treating provider and insurance preference.


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LIST OF ABBREVIATIONS
AE
Adverse Event
ALP
Alkaline Phosphatase
ALT
Alanine Aminotransferase
ANC
Absolute Neutrophil Count
AST
Aspartate Aminotransferase
AUC
Area Under the Curve
BUN
Blood Urea Nitrogen
CBC
Complete Blood Cell (Count)
CDK
Cyclin-Dependent Kinases
CQ
Chloroquine
CR
Complete Response
CRC
Clinical Research Coordinator
CRF
Case Report Form
CSF
Cerebral Spinal Fluid
CT
Computerized Tomography
CTCAE 
Common Terminology Criteria for Adverse Events
CTL
Cytotoxic T Cell
CTO
Clinical Trials Office
DFS
Disease-Free Survival
DLT
Dose-Limiting Toxicity
DSMC
Data and Safety Monitoring Committee
DSMP
Data and Safety Monitoring Plan
ER
Estrogen Receptor
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GVHD
Graft-Versus-Host Disease
HCT
Hematopoietic Cell Transplantation
HGB
Hemoglobin
IP
Investigational Product
IRB
Institutional Review Board
LDH
Lactate Dehydrogenase
MCWCC
Medical College of Wisconsin Cancer Center
MTD
Maximum-Tolerated Dose


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NCI
National Cancer Institute
ORR
Overall Response Rate
PBMC
Peripheral Blood Mononuclear Cells
PD
Disease Progression
PK
Pharmacokinetics
PSGL-1
P-selectin Glycoprotein Ligand-1
PR
Partial Response
RBC
Red Blood Cell (Count)
ROS
Reactive Oxygen Species
SAE
Serious Adverse Event
SD
Stable Disease
SD
Standard Deviation
SRC
Scientific Review Committee
ULN
Upper Limit of Normal
UP
Unanticipated Problem
UPIRSO  
Unanticipated Problems Involving Risks to Subjects or Others


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TABLE OF CONTENTS
PROTOCOL SUMMARY ........................................................................................................... 5 
STUDY SCHEMA ...................................................................................................................... 8 
STUDY CALENDAR.................................................................................................................. 9 
LIST OF ABBREVIATIONS......................................................................................................12 
1 BACKGROUND.....................................................................................................................17 
1.1. PROSTATE CANCER ..........................................................................................................17
1.2 JAK2-STAT5 SIGNALING PATHWAY ......................................................................................17 
1.3 TRANSCRIPTION FACTOR STAT5 AND PC GROWTH:.............................................................18
1.4 GENETIC STAT5 INHIBITION SUPPRESSES AR PROTEIN AND MRNA EXPRESSION IN PC..........19 
1.5 PACRITINIB........................................................................................................................25 
1.5.1  Pharmacology...........................................................................................................................................25
1.5.2 Preclinical Toxicology ..............................................................................................................................25
1.5.3 Summary of Clinical Pharmacology and Phase 1 Studies with Healthy Volunteers with Pacritinib ....26
1.5.4 Overview of Clinical Studies of Pacritinib in Patients with Myelofibrosis ............................26
1.5.5 Rationale for Dosage Selection.................................................................................................................31
2 HYPOTHESIS, OBJECTIVES, AND ENDPOINTS ................................................................32 
2.1 PRIMARY OBJECTIVES .......................................................................................................32 
2.2 SECONDARY OBJECTIVES ..................................................................................................33 
2.3 EXPLORATORY OBJECTIVES...............................................................................................33 
2.4 PRIMARY ENDPOINT ..........................................................................................................33 
2.5 SECONDARY ENDPOINT(S) .................................................................................................33 
2.6 EXPLORATORY ENDPOINTS................................................................................................33 
3 STUDY DESIGN....................................................................................................................33 
3.1 GENERAL DESCRIPTION.....................................................................................................33 
3.2 STUDY COMPLETION .........................................................................................................34 
4 SUBJECT PARTICIPATION, DISCONTINUATION, 
AND WITHDRAWAL ................................................................................................................34 
4.1 SUBJECT STATUS..............................................................................................................34
4.2 PRESCREENING AND SCREENING LOG ................................................................................34
4.3 CONSENT..........................................................................................................................35 
4.4 SCREENING PROCEDURES.................................................................................................35 
4.5 BIOSPECIMEN STUDIES AND PROCEDURES ..........................................................................35 
4.5 ELIGIBILITY CONFIRMATION................................................................................................38 
4.6 DISCONTINUATION OF STUDY TREATMENT, WITHDRAWAL, AND COMPLIANCE........................41 
4.7 LOST TO FOLLOW-UP.........................................................................................................42 
4.8 ACCRUAL SUSPENSION AND CLOSURE................................................................................42 
4.9 END OF STUDY DEFINITION ................................................................................................43 
4.10 STUDY DISCONTINUATION AND CLOSURE..........................................................................43 
5 TREATMENT PLAN ..............................................................................................................43 
5.1 PACRITINIB........................................................................................................................43 
5.1.1 Study Treatment Description and Storage ...............................................................................................43
5.1.2 Dosage, Route, and Mode of Administration...........................................................................................43
5.2 DOSE ADJUSTMENT...........................................................................................................44 


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5.2.1 Treatment Interruption and Discontinuation ..........................................................................................44
5.2.2 Dosage Management Guidelines for Hematologic Toxicity and Related Complications.......................45
5.2.3 Pacritinib Dosage Management Guidelines for QTc Interval Prolongation, Reduction in Ejection 
Fraction, and Other Cardiac Toxicities ............................................................................................................46
5.2.4 Pacritinib Dosage Management Guidelines for Diarrhea.......................................................................48
5.2.5 Pacritinib Dosage Management Guidelines for Pacritinib-Related Nonhematologic Toxicities Other 
than QTc Prolongation, Decreased Cardiac Ejection Fraction, Other Cardiac Toxicities or Diarrhea ........49
5.3 CONCOMITANT AND EXCLUDED THERAPIES.........................................................................49
5.4 DIETARY RESTRICTIONS.....................................................................................................50 
6 ADVERSE EVENTS: DEFINITIONS, COLLECTION 
AND REPORTING REQUIREMENTS ......................................................................................50 
6.1 DEFINITIONS .....................................................................................................................50 
6.1.1 Adverse Event............................................................................................................................................50
6.1.2 Serious Adverse Event (SAE) ...................................................................................................................50
6.1.3 Attribution of an Adverse Event ...............................................................................................................51
6.1.4 Expectedness of an Adverse Event ...........................................................................................................51
6.2 COLLECTION AND REPORTING REQUIREMENTS FOR ADVERSE EVENTS AND SERIOUS ADVERSE         
EVENTS.......................................................................................................................52 
6.2.1 Collection of Adverse Events ....................................................................................................................52
6.2.2 Reporting of Adverse Events and Serious Adverse Events ......................................................................52
6.2.3 Reporting Instructions ..............................................................................................................................53
6.3 UNANTICIPATED PROBLEM INVOLVING RISK TO SUBJECT OR OTHER (UPIRSO) ....................54 
6.4 SUBJECT COMPLAINTS.......................................................................................................54 
7 PHARMACEUTICAL INFORMATION ...................................................................................55 
7.1 PRODUCT DESCRIPTION.....................................................................................................55 
7.2 MECHANISM OF ACTION .....................................................................................................55 
7.3 PRODUCT SUPPLY.............................................................................................................55 
7.4 STORAGE CONDITIONS ......................................................................................................55 
7.5 HANDLING AND DRUG ACCOUNTABILITY..............................................................................55 
7.6 CONTRAINDICATIONS.........................................................................................................56 
7.7 KNOWN ADVERSE EVENTS.................................................................................................56
8 STATISTICAL CONSIDERATIONS.......................................................................................58 
8.1 STUDY POPULATIONS ........................................................................................................58 
8.2 STUDY HYPOTHESES .........................................................................................................58
8.3 STUDY DESIGN AND SAMPLE SIZE........................................................................................58
8.4 ANALYSIS OF PRIMARY ENDPOINT .......................................................................................59 
8.5 ANALYSIS OF SECONDARY ENDPOINTS ................................................................................59 
8.6 ANALYSIS OF EXPLORATORY ENDPOINTS.............................................................................59 
8.7 SAFETY ANALYSES.............................................................................................................59 
8.8 OTHER ANALYSES..............................................................................................................59 
8.9 INTERIM ANALYSES ............................................................................................................60 
8.10 MISSING DATA.................................................................................................................60 
9 DATA AND SAFETY MONITORING PLAN (DSMP) .............................................................60 
9.1 DATA AND SAFETY MANAGEMENT OVERVIEW......................................................................60 
9.2 STUDY TEAM.....................................................................................................................60 
9.3 QUALITY ASSURANCE ........................................................................................................60 
9.4 CLINICAL TRIALS OFFICE....................................................................................................61 
9.5 DSMC..............................................................................................................................61 


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10 REGULATORY COMPLIANCE, ETHICS, AND 
STUDY  MANAGEMENT..........................................................................................................61 
10.1 REGULATORY COMPLIANCE..............................................................................................61
10.2 PRESTUDY DOCUMENTATION ...........................................................................................62 
10.3 INSTITUTIONAL REVIEW BOARD ........................................................................................62
10.4 SUBJECT CONFIDENTIALITY AND ACCESS TO SOURCE DOCUMENTS/DATA ..........................63 
10.5 PROTECTION OF HUMAN SUBJECTS..................................................................................63 
10.5.1 
Protection from Unnecessary Harm ................................................................................................63
10.5.2 
Protection of Privacy ........................................................................................................................64
10.5.3
Changes in the Protocol ...................................................................................................................64
10.6 INVESTIGATOR COMPLIANCE ............................................................................................64
11 DATA HANDLING AND RECORD KEEPING .....................................................................65 
11.1 OVERVIEW ......................................................................................................................65
11.2 DATA MANAGEMENT RESPONSIBILITIES ............................................................................65 
11.3 SOURCE DOCUMENTS......................................................................................................65
11.4 CASE REPORT FORMS.....................................................................................................66 
11.5 STUDY RECORD RETENTION ............................................................................................66 
APPENDIX 1. PERFORMANCE STATUS CRITERIA ..............................................................68 
APPENDIX 2. LOST TO FOLLOW-UP LETTER ......................................................................69 
APPENDIX 3. SELECTED STRONG INHIBITORS OF 
CYP3A4....................................................................................................................................70 
APPENDIX 4. SELECTED STRONG INDUCERS OF 
CYP450 ....................................................................................................................................71 
APPENDIX 5. THE STAGES OF HEART FAILURE, 
NEW 
YORK 
HEART 
ASSOCIATION 
CLASSIFICATION....................................................................................................................72 
APPENDIX 6. MEDICATIONS WITH SIGNIFICANT 
ARRHYTHMOGENIC POTENTIAL ..........................................................................................73 
APPENDIX 7. COMMON TERMINOLOGY CRITERIA 
FOR ADVERSE EVENTS: DIARRHEA (VERSION 5.0)
.................................................................................................................................................78 
APPENDIX 8. INVESTIGATOR RESPONSIBILITIES, 
REQUIRED DOCUMENTATION, AND SIGNATURE ...............................................................79 
APPENDIX 
9. 
COMPRESSIVE 
GERIATRIC 
ASSESSMENT FORMS ...........................................................................................................80 
APPENDIX 10. PILL DIARY.....................................................................................................80 
REFERENCES .........................................................................................................................81


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1 BACKGROUND
1.1. Prostate cancer
Prostate cancer (PC) is the most common non-cutaneous malignancy among elderly men, with 
more than 60% of all PC cases diagnosed in men over 65 years of age. (1) The estimated 
prevalence of PC in men aged 75 years and older is currently more than a million and expected 
to quadruple by 2030, given the long natural history of the disease and aging of the population.
(2, 3) Systemic disease from prostate cancer includes biochemical recurrence (a rise in PSA after 
definitive treatment with no radiographic evidence of disease elsewhere), as well as overt 
metastatic disease confirmed by imaging. Once the disease is systemic, the goal of treatments is 
palliative, and physicians should take into account therapy-related side effects, which can 
adversely affect the quality of life.
-risk subpopulation 
with a significant risk of PC-related mortality. The median PC-specific survival for patients with 
rapidly rising serum PSA is approximately five years, which is comparable to patients with limited 
metastatic castration-sensitive disease (< 4 bone metastases and/or node-only soft tissue 
involvement). 
Intermittent androgen deprivation therapy (ADT) achieved with GnRH agonist or antagonist 
is considered the standard of care for biochemical relapse. Side effects of ADT include but are 
not limited to weakness, osteoporosis, muscle wasting, metabolic syndrome, hot flashes, 
increased risk of diabetes, cardiovascular disease, depression, impotence, falls,
and 
cognitive/mood disorders. (4-7) While these untoward effects are tolerable in the young fit 
population, they lower the quality of life significantly. Importantly, they can have significant 
adverse consequences in elderly cancer patients with preexisting comorbidities and functional 
impairment. (5, 7, 8) Once ADT is initiated for systemic disease, it is usually continued for life.
Given the mechanism of ADT, it is postulated that these effects are a direct result of low 
testosterone. In many elderly men, their testosterone levels do not return to pre-ADT levels after 
ADT is discontinued. Therefore, even a limited trial of ADT may leave them at risk for long-lasting 
adverse effects from hypogonadism. Approximately one-third of patients are deemed high risk for 
side effects and toxicities from ADT. (5) Despite often being asymptomatic from systemic cancer 
and in the absence of a clear survival benefit with early initiation of ADT, older patients continue 
to be subjected to substantial side effects from ADT with a decline in quality of life, falls (due to 
muscle weakness) and exacerbation of underlying chronic diseases (such as heart disease); 
hence there is an urgent and unmet need to explore alternate non-hormonal options for 
PC therapy. 
Our data that are described in the next section support a novel concept that Stat5 is a driver of 
androgen receptor(AR) gene expression in PC, and the Jak2-Stat5 pathway represents a target 
to inhibit expression of diverse AR and AR-V species and thereby control of hormone-sensitive 
and castrate-resistant PC (CRPC) growth.
1.2 Jak2-Stat5 signaling pathway
The Janus kinases (JAKs) are a family of cytoplasmic tyrosine kinases (TYKs) consisting of JAK1,
JAK2, JAK3, and TYK2. They play a pivotal role in the signaling pathways of numerous cytokines,
hormones, and growth factors. Their intracellular substrates include the signal transducer and 
activator of transcription (STAT) family of proteins.


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The JAK/STAT pathways, through the proper actions of the ligands, regulate important 
physiological processes, such as the immune response to viruses, hematopoiesis, lactation, and 
lipid homeostasis. However, dysfunctional signaling caused by a myriad of factors results in 
pathological conditions, such as allergies, asthma, rheumatoid arthritis, severe combined immune 
deficiency, and hematological malignancies. In particular, mutations in the JAK2 gene have been 
associated with myeloproliferative disorders (MPDs), including polycythemia vera (PV), essential
thrombocythemia (ET), and idiopathic myelofibrosis (MF).
The incidence of the JAK2V617F mutation, as determined by an allele-specific polymerase chain 
reaction in granulocytes from patients with MPDs, occurs in 35% to 50% of patients with primary 
MF (PMF), 32% to 57% of patients with ET, and 74% to 97% of patients with PV. This mutation, 
however, can also be found on rare occasions in patients with other chronic myeloid diseases, 
including myelodysplastic syndrome (MDS), MDS/MPDs, and unclassifiable MPD. There is strong 
evidence that the JAK2 mutation (and corresponding continuously active JAK2 tyrosine kinases) 
significantly contributes to the existence and progression of the disease. Its inhibition thus 
presents a suitable target for drug development. Even in patients without JAK2 mutation, the 
JAK/STAT pathway may be deregulated, and these patients may also benefit from JAK2 inhibitor 
therapy.
Stat5 comprises two highly homologous isoforms Stat5a (94 kDa) and Stat5b (92 kDa) (referred 
to as Stat5) which are nucleocytoplasmic proteins acting both as signaling proteins and nuclear 
transcription factors.(9-13) Stat5 becomes activated by phosphorylation of a conserved C-
terminal tyrosine residue(11) by Jak2 tyrosine kinase in PC(14-18) and forms functional dimers 
that translocate to the nucleus and bind to specific Stat5 DNA response elements.(11) Jak2, in 
turn, has a catalytically active kinase domain (JH1) located at the C-terminus juxtaposed to the 
regulatory pseudokinase domain (JH2).(19, 20) Upon cytokine activation, amino acid residues 
Tyr1007/1008 in the activation loop of the JH1 are rapidly autophosphorylated in trans, leading to 
full catalytic activity of Jak2 kinase.(19, 20)
1.3 Transcription factor Stat5 and PC Growth: 
Numerous studies by our team and others have provided the proof-of-concept that Stat5 is an 
inducer of PC growth.(17, 18, 21-41) The blockade of Stat5 signaling induces the apoptotic death 
of PC cells. Conversely, overexpression of active Stat5 induces the proliferation of PC cells in 
culture and promote robustly the growth of PC tumors in mice.(29) In 30–40% of advanced 
CRPCs, the chromosome 17 locus encompassing STAT5A and STAT5B genes undergoes 
amplification, resulting in increased Stat5 protein levels.(29) Notably, high nuclear Stat5 protein 
expression in clinical PCs, at the time of the initial treatment, predicted recurrence of the disease 
in three independent cohorts totaling 1,035 patients.(40, 41) Our recent study shows that 
combined positive status for both Stat5 gene locus amplification and protein expression indicated 
55–60% disadvantage in recurrence-free survival at seven years after radical prostatectomy (RP) 
in univariate analysis and was independently associated with shorter progression-free survival 
(HR=3.62, p=0.021, 95%CI=1.22-10.78) in multivariate analysis, including the CAPRA-S
nomogram variables(42) in a cohort of 300 PC patients treated with RP only.(41) These findings 
demonstrating the predictive value of active Stat5 for clinical PC progression to castrate-resistant 
lethal state(40, 41) illustrate the significance of Stat5 in PC growth and progression in 
patients and corroborate the results in preclinical PC models.(17, 18, 21-38)
While the significance of Stat5 in promoting the growth of PC has been well demonstrated, the 
mechanisms underlying how Stat5 sustains PC cell viability are largely unclear. The effects of 


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active Stat5 signaling on inducing PC cell 
proliferation, 
antagonizing 
apoptosis,
and 
promoting CRPC growth mimic closely those of 
AR effects on PC cells. Our data support a new 
paradigm of Stat5 critically sustaining AR 
mRNA and protein expression in PC. These 
data indicate that Stat5 signaling represents a 
significant driver of AR signaling network and its 
phenotypic effects on PC. Inhibitors of Jak2-
Stat5 signaling may serve as a new class 
AR- antagonists for PC therapy.
1.4 Genetic Stat5 inhibition suppresses AR 
protein and mRNA expression in PC
To investigate whether AR is a Stat5 target 
gene in PC,
Stat5 was inhibited in a 
comprehensive panel of six PC cell lines by 
lentiviral expression of Stat5a/b
targeting 
shRNA (Stat5 shRNA), and the mRNA levels of 
FL-AR, AR-V7 and AR-V9 were evaluated by 
quantitative 
RT-PCR. 
Stat5 
knockdown 
downregulated mRNA levels of both full-length-
AR and the AR splice variants ARV-7 and ARV-
9.  Noteworthy, the degree of AR and AR-V
inhibition achieved by Stat5 knockdown was at 
the same level or higher than direct depletion of
AR with lentiviral expression of AR shRNA in all 
PC cell lines tested (Figure 1). Stat5 
knockdown reduced the mRNA levels of full-
length AR, AR-V7, and AR-V9 by 80-90% in 
eight days after lentiviral Stat5 shRNA 
expression, shown in Figure 1.
We 
further 
evaluated 
whether 
Stat5 
suppression of AR mRNA levels leads to 
downregulation of AR protein levels in PC. 
Figure 2 shows that genetic depletion of 
Stat5a/b by lentiviral expression of Stat5 
shRNA resulted in reduced AR protein 
expression in all PC cell lines tested.
Genetic knockdown of Stat3 did not affect 
AR mRNA levels (data not shown), indicating this effect is specific to Stat5. 
Given that inhibition of Stat5 in PC resulted in downregulation of AR expression in PC, we next 
tested whether activation of Stat5, in turn, upregulates AR expression in PC. Constitutively active 
mutants of Stat5a/b (CAStat5a/b; Stat5aS710F, Stat5bS715F)(18) were lentivirally expressed in 
Fig.1. Stat5 knock-down depletes AR mRNA expression in PC 
cells. Stat5a/b was inhibited by lentiviral expression of Stat5a/b 
shRNA (shStat5a/b) or non-target shRNA (shCtrl) in PC cell lines 
for 72 h, followed by RNA extraction and quantification of FL-AR, 
AR-V7 and AR-V9 mRNA levels by qRT-PCR.
Fig. 2. Stat5 drives AR protein expression in PC cells. 
Immunoblotting (IB) of AR in PC cells 72 h after lentiviral expression of 
Stat5 shRNA (shStat5a/b) vs. control shRNA (shCtrl). Effective genetic 
depletion of Stat5a/b and equal loading are demonstrated by IB with 
anti-Stat5a/b and anti-actin antibodies of whole cell lysates (WCLs), as 
indicated.


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a panel of six PC cell lines, and mRNA levels of 
full-length AR and AR splice variants (AR-V7, AR-
V9) were determined by quantitative RT-PCR.
Expression of CAStat5a/b resulted in a uniform 
increase in mRNA levels of full-length AR, AR-V7,
and AR-V9 in all PC cell lines tested, as shown in 
Figure 3. Furthermore, expression of CAStata/b 
resulted in a robust increase in AR protein expression in all PC cell lines tested, shown by 
immunoblotting in Figure 4. In summary, our data show that active Stat5 induces FL-AR and 
AR-V mRNA levels resulting in robustly increased AR protein expression in both androgen 
sensitive and CRPC.
We next sought to evaluate if Stat5 regulation of AR mRNA and protein levels is evident in an in 
vivo setting where PC cells were grown as xenograft tumors in mice. CWR22Pc cells (1.5×107) were 
inoculated subcutaneously (s.c.) into the flanks of nude mice. After tumors reached ~100 mm3 in size 
(12 d), mice were treated with a specific Stat5 inhibitor IST5-002(24) (40 mg/kg; i.p.) or vehicle (0.3% 
hydroxypropyl cellulose/H2O) (5 mice/group). AR mRNA and protein levels were evaluated by q-RT-
PCR(43) and by immunohistochemistry (IHC), as previously described.(39-41, 44, 45) As shown in 
Figure 5, suppression of Stat5 by IST5-002 resulted in a marked decrease in AR mRNA and protein 
expression in PC xenograft tumors in vivo.
Fig. 3. Active Stat5 induces a robust increase in AR mRNA 
levels in both androgen sensitive and CRPC cells. Stat5a/b 
signaling was increased by lentiviral expression of constitutively 
active (CA) Stat5a/b or GFP (control) for 72 h in PC cell lines 
followed by RNA extraction and quantification of FL-AR, AR-V7 
and AR-V9 mRNA levels by qRT-PCR.
Fig.4. Active Stat5 induces a robust increase in AR protein 
levels in PC cells. Stat5a/b signaling was increased by 
lentiviral expression of constitutively active (CA) Stat5a/b or 
GFP (control) for 72 h in PC cell lines followed by IB analysis of 
AR protein levels. Increased active Stat5a/b levels and equal 
loading are demonstrated by IB with anti-Stat5pY mAb and anti-
actin pAb of WCLs.
Fig.5. Pharmacological Stat5 inhibition decreases AR 
protein and mRNA levels in PC xenograft tumors in nude 
mice. Nuclear AR and Stat5 levels were detected by 
immunostaining of paraffin-embedded tissue sections of 
CWR22Pc tumors from mice treated with IST5-002 (IST5) 
(40 mg/kg; i.p.) for 40 days. AR mRNA levels were evaluated 
by qRT-PCR.


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In conclusion, these data indicate that Stat5 is a critical inducer of full-length AR and AR-
V7 mRNA expression not only in cell culture models of PC but also in PC xenograft tumors 
grown in vivo in mice.
Pharmacological Jak2 inhibition:
The discovery and identification of the Jak2V617F mutation causing constitutive activation of 
Jak2 in patients with myeloproliferative disorders (MPDs)(46-50) triggered the development of small-
molecule Jak2 inhibitors to specifically target hyperactive Jak2 signaling. Predominantly utilizing 
structure-based drug design, the current Jak2 inhibitors target both wild-type Jak2 and the mutated 
Jak2 in an ATP-competitive manner occupying the ATP-binding pocket.(51) This is termed Type I 
mode of inhibition which stabilizes the kinase in its active conformation.(52) Numerous Type I Jak2 
inhibitors differing in structure, specificity against wild-type vs. mutated Jak2, and selectivity for 
different Jak family members, are at different stages of clinical development.(51) CHZ686 is a Type 
II Jak2 inhibitor, which binds Jak2 in the inactive conformation, where the inhibitor occupies the ATP 
binding site and an induces hydrophobic pocket stabilizing the conformation.(52) CHZ686 is not in 
clinical development. 
       Ruxolitinib (53-55) is a first-in-class, orally available Type I inhibitor of Jak1 and Jak2 which is 
FDA approved for MPDs and is currently being tested for efficacy in rheumatoid arthritis (RA) and 
psoriasis.(51) AZD1480 (56) is a potent early Jak1/2 inhibitor which, unfortunately, was withdrawn 
from clinical development because of neurotoxicity. Baricitinib (57) is another first-generation Jak1/2 
inhibitor, which is structurally related to RUXO with predominant indication for RA and psoriasis (58).
New generation Type I Jak2 inhibitors include momelotinib, (59) gandotinib,(60) fedratinib, (61-65)
and pacritinib
(66-72). Fedratinib
is currently FDA approved for MPDs, and pacritinib
(NCT03165734), momelotinib (NCT04173494) and gandotinib (NCT01594723) are being tested in 
phase III trials for MPDs. 
Fig.6a. Ruxolitinib (RUXO) does not effectively suppress Jak2-Stat5 signaling, AR levels and PC cell viability in PC cells. 
CWR22Rv1 and CWR22Pc PC cells were treated with RUXO at 0.6 µM for 3 days followed by RNA extraction and quantification 
of FL-AR, AR-V7 and AR-V9 mRNA levels by qRT-PCR. PC cells with lenti-viral expression of shAR were used as control for the 
q-PCR of AR regulation. Analysis of the Stat5 activation was analyzed by immunoprecipitation of Stat5 followed by immunoblotting 
with anti-pYStat5 ab and the AR protein levels were evaluated by immunoblotting of whole cell lysates (WCL) with anti-AR ab. 
Equal loading is demonstrated by IB with anti-Stat5a/b and anti-actin antibodies of whole cell lysates (WCLs).
AR protein levels was conducted by immunoprecipitation (IP) and immunoblotting (IB). Equal loading is demonstrated by IB with
anti-Stat5a/b and anti-actin antibodies of whole cell lysates (WCLs).


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Pacritinib
was 
tested 
for 
efficacy in non-small cell lung
cancer
(NSCLC)
(NCT02342353), but the trial 
was terminated because of 
drug shortage. In addition, 
Pacritinib has been tested in 
phase II trial for refractory 
colorectal cancer
(NCT02277093) but the trial
was terminated because of 
lack of efficacy(73).
The key adverse effects noted 
in this trial included nausea, 
abdominal discomfort,
constipation and fatigue.(73)
Of the other Type I Jak2 
inhibitors, both ruxolitinib and 
momelotinib have been tested 
for efficacy in solid tumors 
(NCT0063878;03274778; 
03878524;02711137; 
02101021;02244489; 
02206763; 02258607);
these
were terminated due to lack of 
efficacy. Specifically, ruxolitinib 
displayed no efficacy in a phase 
II trial in metastatic
CRPC 
(NCT0063878). However, it is 
important 
to 
note 
that 
the 
potency 
of 
ruxolitinib 
and 
momelotinib 
against 
cells 
expressing wild-type Jak2 vs. the 
mutated Jak2V617F is largely 
unclear. Clinical PC does not to 
harbor 
the 
Jak2V617F 
mutation,(74) which explains our 
findings 
showing 
that 
both 
ruxolitinib and momelotinib (data 
not shown) are very weak 
inhibitors of Jak2-Stat5 pathway 
in PC (Figure 6 a and b). At the 
same time, our data show potent suppression of Jak2-Stat5 pathway in PC by pacritinib
(Figures 7–10), which makes pacritinib an excellent candidate for therapy development for 
recurrent PC.
As shown in Figure 6b, we compared the efficacy of pacritinib vs. ruxolitinib to suppress PC cell 
viability vs. androgen deprivation (-DHT), lenti-shStat5, lenti-shJak2 or lenti-shAR. Treatment of 
CWR22Pc PC cells with 600 nM pacritinib (PAC) led to remarkable decrease in the fraction of 
viable PC cells after five days of exposure to pacritinib (PAC). At the same time, similar treatment 
Fig.6b. Treatment of PC cells with Ruxolitinib (RUXO) (600 nM) did not affect 
PC cell viability when compared to treatment of the cells with Pacritinib (PAC) 
(600 nM), which decreased the fraction of viable CWR22Pc PC cells more 
effectively than androgen deprivation (-DHT), lenti-shJak2, lenti-shStat5 or 
lenti-shAR. Attached viable cells were visualized by crystal violet staining and 
counting (graphs). 
Fig.7. Expression of constitutively active Stat5 (CASTat5) counteracts the 
effect of Pacritinib in reducing PC cell viability. CAStat5 was lentivirally 
expressed in CWR22Pc PC cells for 3 days prior to treatment of the cells with 
Pacritinib at 300 or 600 nM concentrations for 3 days. Attached viable cells were 
visualized by crystal violet staining and counting (graphs). 


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of the PC cells with ruxolitinib (600 nM) did not affect the viability of the cells. Importantly, 
pacritinib, lentiviral expression of shStat5 or shJak2 (vs. shCtrl) were all significantly more robust 
inducers of cell death than androgen deprivation itself (-DHT) or lentiviral expression of shAR in 
PC cells (Figure 6b). At the same time, lentiviral expression of constitutively active Stat5 
(CAStat5) abolished the growth suppression induced by pacritinib in PC cells (Figure 7). 
To evaluate the efficacy of PAC in suppressing AR in PC models, PC cell lines were treated 
with different concentrations of PAC. Jak2 activity was inhibited by Jak2 inhibitor pacritinib (PAC)
in PC models. (71, 72, 75, 76). Pharmacological Jak2 inhibition by pacritinib caused a dose-
dependent reduction in both FL and AR-V AR mRNA and protein levels in CWR22Rv1 and CWR22Pc 
PC cell lines (Figure 8). Furthermore, we compared the potency of research grade pacritinib
(MedChem Express) vs. clinical grade pacritinib in suppressing AR mRNA and protein expression 
in PC cells lines.
The clinical grade 
pacritinib showed 
greater potency in 
suppressing 
AR 
mRNA and protein 
expression in PC 
cells compared to 
the 
research 
grade 
pacritinib,
likely due to the 
purity level of the 
compound
(Figure
8).
Of
note, 
similar 
to 
pacritinib, 
other 
Jak2 
inhibitors,
such as AZD1480, 
gandotinib 
and 
baricitinib, 
all 
suppress 
Stat5 
and AR levels in 
PC cells (data not 
shown). 
To evaluate if 
Jak-Stat5 inhibition 
suppresses 
AR 
mRNA and protein 
levels in clinical 
patient-derived 
PCs, we utilized ex 
vivo PC tumor explant culture model we have previously established. (17, 18, 39, 77-83) In essence, 
the finding of Stat5 regulating AR mRNA in PC cell lines was recapitulated in patient-derived PC 
tissues cultured ex vivo in 3D tumor explant cultures for seven days in the presence or absence of 
the Stat5 inhibitor IST5-002(24) or the Jak2 inhibitor PAC. As shown in Figure 8, both FL-AR and AR-
V7 mRNA levels were decreased in 3D tumor explants by either IST5-002 (patients nos. 1 and 2) or 
Fig. 8. Pharmacological inhibition of Jak2-Stat5 by Pacritinib suppresses AR mRNA and protein 
levels in PC cells. The clinical grade Pacritinib (PAC) (from CTI-BioPharma; CTI) is more potent in 
suppressing androgen receptor (AR) mRNA and protein expression in prostate cancer (PC) cells than the 
research grade PAC from MedChem Express (MCE). CWR22Pc and CWR22Rv1 cells were treated with 
PAC (CTI vs. MedChem Express) for 3 days at indicated concentrations followed by RNA extraction and 
quantification of FL-AR, AR-V7 and AR-V9 mRNA levels by qRT-PCR. PC cells with lenti-viral expression 
of shAR were used as control for the q-PCR of AR regulation. Analysis of the AR protein levels was 
conducted by immunoprecipitation (IP) and immunoblotting (IB). Equal loading is demonstrated by IB with 
anti-Stat5a/b and anti-actin antibodies of whole cell lysates (WCLs).


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PAC (patient no. 3). Collectively, these data indicate that 
Jak2-Stat5 axis is critical for FL- AR and AR-V7 mRNA
expression not only in cell culture or xenograft PC tumor 
models of androgen sensitive and CRPC, but also in clinical 
patient-derived PCs. 
In order to investigate whether the regulatory effect of 
pacritinib on AR mRNA and protein expression is mediated 
by Stat5, we first overexpressed constitutively active Stat5 
(CAStat5) vs. GFP by lentivirus in PC cells for three days 
followed by pacritinib treatment of the cells for three days. As 
shown in Figure 9, expression of active Stat5 entirely 
abolished the suppressive effect of pacritinib on AR protein 
and mRNA expression in PC cells. In parallel experiments, 
we evaluated if pacritinib is able to further reduce AR protein 
and mRNA expression after genetic depletion of Stat5. In 
these experiments, Stat5 levels were suppressed by lentiviral 
expression of shStat5 for three days followed by pacritinib
treatment for three days (Figure 10). The data show that 
pacritinib did not further reduce AR levels after genetic 
depletion of Stat5 in PC cells (Figure 10). In summary, 
these data indicate that the regulatory effects of 
pacritinib on the AR mRNA and protein levels in PC cells 
are mediated by Stat5. 
            In conclusion, pharmacological inhibition of 
Jak2-Stat5 signaling by pacritinib results in extensive 
Fig. 9. Pacritinib does not further reduce AR mRNA and protein levels 
in PC cells after genetic depletion of Stat5. Stat5 was genetically 
down-regulated by lentiviral expression of shStat5 vs. shCtrl for 48 h 
followed by Pacritinib treatment of the cells for 72 h. Immunoblotting 
(IB) of AR in PC cells 72 h after lentiviral expression of Stat5 shRNA 
(shStat5a/b) vs. control shRNA (shCtrl). Stat5 and AR protein levels were 
evaluated by IP and immunoblotting. FL-AR, AR-V7 and AR-V9 mRNA 
levels were determined by qRT-PCR.
Fig.8. Inhibition of Stat5 by IST5-002 or PAC
suppress AR mRNA levels in patient-derived 
PCs cultured ex vivo.
Clinical PCs
(n=3)
obtained from prostatectomies were cultured for 7 
days ex vivo in 3D tumor explant cultures in the 
presence of Stat5 inhibitor IST5-002 (12.5 µM) or 
PAC (1 µM) vs. vehicle. AR mRNA levels were 
analyzed by q-PCR. 
Fig. 10. Expression of constitutively active 
Stat5 (CAStat5) counteracted the Pacritinib-
induced suppression of AR mRNA and protein 
expression in prostate cancer cells. CAStat5 
vs. GFP were lentivirally expressed in PC cells for 
72 h prior to treatment of the cells with PAC at 
indicated concentrations for 72 h. Stat5 and AR 
protein levels were evaluated by IP and 
immunoblotting. FL-AR, AR-V7 and AR-V9 
mRNA levels were determined by qRT-PCR.


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death of PC cells. Specifically, pacritinib-induced loss of PC cell viability is greater than 
that of androgen deprivation. These data provide a solid scientific background for the 
clinical trial described here.
1.5 Pacritinib 
Pacritinib is a novel JAK2/fms-like receptor tyrosine kinase 3 (FLT3) inhibitor that has 
demonstrated promising antitumor activity in two mouse models of human malignancies. 
Preclinical toxicology studies have identified a safe starting dosage for clinical studies. The 
potential indications that may be targeted include (i) PV, ET, and MF, all of which are MPDs with 
a high frequency of a JAK2V617F mutation;(ii) certain leukemias and lymphomas where other 
forms of JAK aberrations have been reported; and (iii) acute myeloid leukemia, in which FLT3 
inhibitors have shown preliminary clinical promise.
1.5.1  Pharmacology
Pacritinib is a potent, selective inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory
concentration.[IC50=23 nM and 22nM respectively) as well as JAK2V617F mutant kinase activity
(IC50=19 nM). Pacritinib is also a potent inhibitor of cellular proliferation in human leukemia and 
lymphoma cell lines selected for their dependence on the target kinases. Consistent with these 
activities, exposure to pacritinib resulted in the reduction of phospho-JAK2, phospho-STAT3, or 
phospho-STAT5 in the relevant cell lines.
Pharmacokinetics in Animals
Pharmacokinetics (PK) following single intravenous (i.v.) or oral administration of pacritinib were
evaluated in mice, rats, and dogs. Following oral administration, pacritinib showed rapid 
absorption in mice (time of maximum concentration [Tmax] from 0.5 to 1.3 hours) and moderately 
fast absorption in rats and dogs (Tmax ~4 hours). The oral terminal half-lives were 2.2, 5.7, and 
4.4 hours in mice, rats, and dogs, respectively. As measured by liver blood flow, the systemic 
clearance of pacritinib from plasma was high in mice (8 L/h/kg) and dogs (1.6 L/h/kg) and 
moderate in rats (1.6 L/h/kg). The i.v. terminal half-lives were 5.6, 6, and 4.6 hours in mice, rats, 
and dogs, respectively. The oral bioavailability of pacritinib was 39% in mice, 10% in rats, and 
24% in dogs
1.5.2 Preclinical Toxicology
The adverse effects of pacritinib were evaluated in 30-day repeated oral dose toxicity studies with 
14-day recovery in both mice and dogs, and in 26- and 39-week chronic toxicity studies in mice 
and dogs, respectively. Key findings included dose-dependent leukopenia accompanied by 
neutropenia (dog) and neutrophilia (mice) that partially reversed during recovery. Mice also 
showed dose-dependent but reversible thrombocytosis and anemia. In the chronic toxicity 
studies, low magnitude decreases in neutrophils and RBC parameters were observed. No 
treatment-related hepatic changes were observed. with the exception of increased aspartate 
transaminase (to +109%, male dogs) and increased triglycerides (to +57%, male and female 
dogs).
In the 30-day study in dogs, animals receiving mid and high dosages of pacritinib experienced 
vomiting and diarrhea that increased in severity despite treatment with antiemetic and 
antidiarrheal medication. Similarly, in the 39-week study in dogs, an increased incidence of 


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nausea and vomiting was observed at dosages of 20 mg/kg/day and higher. Periods of low food 
consumption in individual animals receiving 40 and 50 mg/kg/day were accompanied by rapid 
weight loss (which was controlled and reversed with subcutaneous fluid and supplemental food) 
and were considered treatment related and adverse. Based on these studies, the no observed 
adverse effect level was determined to be 100 mg/kg BID in mice and 10 mg/kg BID in dogs.
1.5.3 Summary of Clinical Pharmacology and Phase 1 Studies with Healthy Volunteers 
with Pacritinib 
To date, the Sponsor has completed two PK studies for pacritinib in healthy volunteers, including 
a food effect study (SB1518-2010-006) characterizing the effects of a high calorie, high-fat meal 
on the bioavailability and PK of pacritinib and a study assessing inter- and intra-individual 
variability of oral pacritinib in healthy volunteers under fasted conditions at 100 mg, 200 mg and 
400 mg doses (SB15182010-004). Also, the single and multiple-dose population PK of pacritinib 
has been characterized following multiple-dose administration of pacritinib in two studies 
(SB1518-2007-001 and SB1518-2008-003) in patients with advanced myeloid malignancies. 
After the administration of single doses of pacritinib in a randomized, three-treatment, three-period 
crossover study (SB1518-2010-004) in healthy volunteers under fasting conditions, peak plasma 
concentrations were reached at a median Tmax ranging from 4.5 to 5.5 hours across the 100 to 
400 mg dose range. While between-patient variability was relatively high (28% to 45%), the within-
patient variability was low (13% to 15%), highlighting the consistent systemic exposure for 
pacritinib in individual patients. The mean elimination half-life was approximately 34 hours and 
was not dependent on dose. The systemic exposure of pacritinib in healthy volunteers was 
comparable to that in patients. After oral administration of single 200-mg doses (2×100 mg 
capsules) of pacritinib under fed and fasted conditions in study SB1518-2010-006, the 90% 
confidence intervals for the geometric mean ratios (fed to fasted) for maximum concentration 
observed (Cmax), area of the curve up to the last measurable concentration (AUC0-t), and area 
under the curve to infinite time (AUCinf) were between 80% and 125%, demonstrating lack of an 
effect of food on absorption. Given this data, pacritinib can be orally administered without regard 
to timing of meals. 
Pooled analyses of PK assessments from the two completed clinical studies in patients at 
pacritinib dosages up to 600 mg once daily (QD) showed slow absorption (Tmax four to six hours) 
and dose-related increases in systemic exposure up to 400 mg QD. The rate of absorption was 
linear at doses up to 300 mg and thereafter appeared to be rate limited. Therefore, modeling 
suggested that, at doses of over 200 mg per day, divided doses would yield increased steady 
study blood levels. Beyond the 400 mg QD dosage, there was a minimal increase in exposure 
with doses up to 600 mg QD suggesting an involvement of a saturable process in oral absorption 
of pacritinib. In addition, the results demonstrated a prolonged elimination half-life (mean Day 1 
half-life=47 hours), supporting a QD regimen of pacritinib in clinical development. Comparison of 
systemic exposure of pacritinib on Days 1 and 15 showed a 1.5- to 2-fold increase in systemic 
exposure at steady state.
1.5.4 Overview of Clinical Studies of Pacritinib in Patients with Myelofibrosis 
Approximately 967 individuals have received pacritinib in 15 completed studies, which includes 
552 patients with myelofibrosis who were assigned to a pacritinib arm. Completed studies include 
two controlled studies in myelofibrosis, four uncontrolled clinical studies in cancer patients, and 


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nine clinical pharmacology/pharmacokinetic studies. The summary below describes efficacy and 
safety observations from across the completed controlled (phase 3) studies in myelofibrosis. 
Phase 3 Myelofibrosis Study 
PERSIST-1 was the first phase 3 study of pacritinib, comparing the efficacy of 400 mg QD with 
best available therapy (not including ruxolitinib) in patients with PMF, PPV-MF, or PET-MF. 
Patients previously treated with JAK2 inhibitors were excluded. There were no exclusion criteria 
based on platelet count. Three hundred twenty-seven patients (327) were randomized in a 2:1 
allocation to pacritinib or best available therapy (BAT). PERSIST-1 demonstrated a statistically 
significant improvement in the primary endpoint of percent of pacritinib-treated patients achieving 
5% reduction in spleen volume at Week 24 compared to baseline, as assessed by centrally 
read MRI or computed tomography [CT] imaging), compared to best available therapy. Pacritinib 
efficacy in SVR response was not affected by baseline thrombocytopenia (<5
-to-
respectively), although statistical significance could not be determined in accordance with the pre-
specified statistical analysis plan. More patients treated with pacritinib had improved MF-related 
compared to baseline, as assessed by Myeloproliferative Neoplasm-Symptom Assessment Form 
Total Symptom Score version 2.0 (MPN-SAF TSS 2.0) than those treated with BAT, but this trend 
was not statistically significant. In general, safety was similar to that seen in early phase studies, 
although interim OS results were consistent with a negative trend in survival in pacritinib-treated 
patients, and there were imbalances in fatal and life-threatening events, including intracranial 
hemorrhage, and arrhythmias including sudden death. 
PERSIST-2 was the second phase 3 study of pacritinib, comparing the efficacy of 400 mg QD 
and 200 mg BID with the best available therapy, including ruxolitinib, in patients with PMF, PPV-
MF, or PET-
. Patients previously 
treated with JAK2 inhibitors were included. There were no exclusion criteria based on platelet 
count. Three hundred eleven patients (311) were randomized in a 1:1:1 ratio to the three treatment 
arms. Due to Full Clinical Hold on February 8, 2016, only 211 of the accrued patients were 
evaluable in the ITT (efficacy) population, having been randomized with sufficient time to reach 
the Week 24 evaluation window, thus limiting the power to detect differences in the efficacy 
endpoints. 
PERSIST-2 demonstrated a statistically significant improvement in the coprimary endpoint 
comparing the pooled pacritinib arms with the BAT arm for the percent of pacritinib-treated 
baseline (SVR 
response), as assessed by centrally read MRI or CT imaging, compared to best available therapy 
(18.1% vs. 2.8%, p=0.0011). More patients in the pooled pacritinib had improved MF-related 
symptomatology, meeting the predefined TSS response def
compared to baseline, as assessed by MPN-SAF TSS 2.0, TSS response) than those treated 
with BAT, but this trend in the second co-primary endpoint was not statistically significant (24.8% 
vs. 13.9%, p=0.791). Comparing the individual pacritinib treatment arms to BAT, SVR response 
was nominally significant for BID (21.6%) vs. BAT (p=0.0007), and for QD (14.7%) vs. BAT 
(p=0.0173).
Unlike the pooled coprimary analysis, the BID arm had nominal significance for TSS response vs. 
BAT (32.4% vs. 13.9%, p=0.0106), but the QD arm did not (17.3%, p=0.6524). Exploratory 
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BAT patients, more pacritinib-treated patients achieved the SVR response than patients treated 
with either ruxolitinib or other BAT agents (QD 11/75, 14.7%; BID 16/74, 21.6%; ruxolitinib 1/32, 
3.1%; other BAT 1/40, 2.5%). Similarly, more pacritinib 200 mg BID (but not 400 mg QD) patients 
achieved the MPN-SAF TSS2.0 response (pacritinib 24/74, 32.4% vs. ruxolitinib 6/32, 18.8%), 
despite the increased effect of ruxolitinib compared to all other BAT patients (4/40, 10%). 
Interim analyses of the PERSIST-2 study led to Full Clinical Hold due to interim OS results in 
which the pooled pacritinib treatment arms (QD + BID) were compared with BAT and concerns 
about fatal intracranial hemorrhage, cardiac failure, and cardiac arrest. Updated analyses based 
on the locked database demonstrated that the QD dosing arm had a survival decrement
compared to BAT (hazard ratio [HR]=1.18; p=0.6615), but the BID dosing arm had a trend for 
survival benefit (HR=0.68; p=0.3458). 
In general, the safety observed in PERSIST-2 was similar to that observed in PERSIST-1, 
although differences were seen between the QD and BID pacritinib dosing arms. Except for
hemorrhage, BID dosing generally was associated with lower rates of adverse events (AEs), 
including grade 3/4 and fatal events. The pacritinib BID arm had greater apparent efficacy for both 
SVR and reduction in TSS than either pacritinib dosed at 400 mg QD or BAT. Based on these 
efficacy data, the dose of 200 mg BID has been selected as the upper-level dosage regimen for 
the current dose-ranging study. 
Most relevant to the current study, the safety impacts of prior JAK2 inhibitor treatment in 
PERSIST-2 were compared to patients who did not have such prior treatment. Incidences of 
treatment-emergent AEs (TEAEs) overall followed a similar pattern in the prior JAK2 inhibitor 
treatment and no prior JAK2 inhibitor treatment subgroups in the pacritinib and BAT treatment 
arms (pacritinib, 98.1%, and 96.3%, respectively; BAT, 90.4% and 87.0%, respectively), with a
comparable incidence in the QD and BID dosing arms. While thrombocytopenia showed similar 
rates between subgroups, anemia was increased in the no prior treatment group (pacritinib, 
15.5% [13.5% QD and 17.6% BID] and BAT, 11.5% in the prior treatment group, and pacritinib, 
35.5% [42.3% QD and 29.1% BID] and BAT, 19.6% in the no prior treatment group). Diarrhea, 
nausea, and vomiting had increases in incidence in the prior treatment group compared to the no 
prior treatment group. 
The percentages of patients who experienced TEAEs of CTCAE grade 3 in the pacritinib QD + 
BID pooled arms and BAT arms were 35.9% and 26.9%, respectively, in patients with prior 
treatment and 36.4% and 28.3%, in patients with no prior treatment. When comparing the
incidence of grade 3 events in the QD and BID arm in each subgroup, there was an increased 
incidence of events in the QD arm in the prior treatment subgroup (44.2% compared to 27.5%) 
and an increased incidence of events in the BID arm in the no prior treatment subgroup (40.0% 
the pacritinib and BAT arms were 70.9% and 42.3%, respectively, in patients with baseline prior 
treatment and 74.8% and 56.5% respectively, in patients with baseline no prior treatment. 
The rates of grade 3/4 TEAEs in the QD and BID pacritinib groups were similar to those observed 
in the pacritinib QD + BID pooled arms. The rates of grade 3/4 thrombocytopenia and more 
notably, anemia events were decreased in the prior treatment group (prior treatment: pacritinib, 
12.6% [QD 11.5% and BID 13.7%] and BAT, 9.6%; no prior treatment: pacritinib, 35.5% [QD 
42.3% and BID 29.1%] and BAT, 19.6%). Fatal TEAEs occurred at modestly higher rates in the 
prior treatment group compared to the no prior treatment group in the pacritinib arms, particularly 
in the pacritinib QD arm, (12.6% [QD 17.3% and BID 7.8%] compared to 9.3% [QD 11.5% and 


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BID 7.3%]). The BAT arm showed a reverse pattern, with fatal events increased in the no prior 
treatment group compared to the prior treatment group (13.0% versus 5.8%). 
Adverse Events in the Myelofibrosis Population
Overall, amongst the MF subjects treated with pacritinib in the completed controlled and 
uncontrolled studies, 96% experienced a treatment-emergent AE. The most common TEAEs (> 
10% of subjects) occurred in the SOCs of gastrointestinal disorders (including diarrhea [66%], 
nausea [37%], vomiting [24%], abdominal pain [16%] and constipation [13%]), blood and 
lymphatic system disorders (including anemia [28%] and thrombocytopenia [25%]) and general 
disorders (fatigue [22%], pyrexia [12%] and decrease appetite [13%]). Events of dizziness (10%), 
dyspnea, epistaxis, and pruritus (all 11%) were also observed. 
The most commonly (>10% of all subjects) reported treatment-related TEAEs by the preferred 
term, were in the SOC of gastrointestinal disorders including diarrhea (62%), nausea (31%) and 
vomiting (18%), and the SOC of blood and lymphatic system disorders, including 
thrombocytopenia (16%) and anemia (15%). While GI-related events were common, they were 
generally reversible, of low grade, and rarely led to treatment discontinuation. The potential risk 
of hypersensitivity reaction with pacritinib is low. Pacritinib is contraindicated in patients with a 
known hypersensitivity to the active substance or any of the excipients. Potential mechanisms 
include an immune-mediated response to pacritinib or any of the excipients of the product.
Summary of the PAC203 Phase 2 Dose-Finding Study in Myelofibrosis
The fully enrolled phase 2 component of Study PAC203 is a dose-finding study in patients with 
primary or secondary MF (Dynamic International Prognostic Scoring System [DIPSS] risk score 
of Intermediate-1 to High Risk) who experienced intolerance or treatment failure with ruxolitinib. 
The patient population in Study PAC203 was selected in recognition of safety concerns 
concerning pacritinib that were brought to light during the PERSIST-1 and -2 studies to balance 
the potential for risk with the unmet medical need in patients who failed to achieve or maintain 
benefit from the only approved agent for MF.
Patients who are refractory to ruxolitinib are likely to have high molecular risk disease and poor 
survival (median: 13 to 14 months) (Newberry et al 2017; Kuykendall et al 2018; Pacilli et al 2018). 
As such, these patients have a lower likelihood of achieving SVR and overall poor prognosis. 
Enrollment was not restricted based on platelet count. The primary objective of the study is to 
determine the optimal dosage of pacritinib, spanning the dose-response curve for safety and 
efficacy established in previous phase 1/2 clinical studies and the phase 3 PERSIST-1 and -2
studies.
Patients were randomized 1:1:1 to 200 mg pacritinib BID, 100 mg pacritinib BID, or 100 mg 
pacritinib QD, and randomization was stratified by geographic region and baseline platelet count.
A total of 165 patients were randomized in the phase 2 portion of Study PAC203, and 161 (97.6%) 
patients received any treatment with pacritinib. Median platelet count was 55,000//µL and 76% 
met criteria for ruxolitinib failure, 73% for ruxolitinib intolerance, and 50% for both.
PAC203 Phase 2 Safety Observations
The most common treatment-emergent non-hematologic AEs were GI, including diarrhea (23.6%) 
and nausea (23.6%), and were distributed similarly across treatment arms. The most common 
hematologic AEs were thrombocytopenia and anemia, both occurring at higher frequencies in the 


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200 mg pacritinib BID group (35.2% and 24.1%, respectively); this did not, however, lead to higher 
rates of grade 3 /4 hemorrhage at higher doses (200 mg pacritinib BID: 5.6%; 100 mg pacritinib 
BID: none; and 100 mg pacritinib QD: 7.7%). A slightly higher percentage of patients in the 200 
mg pacritinib BID group had grade 3 or 4 TEAEs (74.1%) compared with the other treatment 
groups, possibly due to higher rates of thrombocytopenia and anemia at baseline in the 200 mg 
pacritinib BID group compared with the other treatment groups. Across the treatment groups, no 
notable shifts from Baseline to a higher worst post-baseline grade were observed for hemoglobin, 
platelets, leukocytes, neutrophils, lymphocytes, or partial thromboplastin time (PTT). The 
incidence of clinically significant laboratory abnormalities was low across the treatment groups.
Overall, 19.3% of patients had a TEAE leading to study drug interruption, and the incidence was 
higher in the 200 mg pacritinib BID group compared with the other treatment groups. The most 
common TEAE leading to study drug interruption was thrombocytopenia (3.7%). The most 
common type of TEAE leading to study drug interruption was in the system organ class of 
infections and infestations (5.6% overall); the incidence was higher in the 200-mg pacritinib BID 
group (11.1%) compared with the other treatment groups (100-mg pacritinib BID group: 5.5%; 
100 mg pacritinib QD group: none). One of the infections was an opportunistic infection (herpes 
esophagitis in the 200 mg pacritinib BID group). Altogether, 17.4% of patients had a TEAE leading 
to study drug discontinuation, and the incidence was higher in the 100 mg pacritinib BID group 
compared with the other treatment groups. The most common TEAE leading to study drug 
discontinuation was thrombocytopenia (3.7% overall).
Grade 3 or 4 TEAEs were reported by 104 patients (64.6%), and the most common TEAEs 
(>10%) by worst grade 3 or 4 were thrombocytopenia (20.5%) and anemia (12.4%). The incidence 
of grade 3 or 4 thrombocytopenia and anemia was higher in the 200 mg pacritinib BID group 
compared with the other treatment groups. However, dose modifications due to thrombocytopenia 
and anemia occurred in all arms; rates of discontinuation due to these events were low overall 
but slightly more common at higher doses: 
Overall, 39.8% of patients had an SAE and the incidence was higher in the 200-mg pacritinib BID 
group (46.3%) compared with the other treatment groups (100-mg pacritinib BID: 36.4%; 100-mg 
pacritinib QD: 36.5%). Overall, the most common SAEs were pneumonia (5.6%), pyrexia (5.0%), 
dehydration (3.1%), sepsis (2.5%), and urinary tract infection (2.5%). The most common SAEs in 
the 200-mg pacritinib BID group were in the system organ class of infections and infestations. A
total of 15 patients (9.3%) died on the study, of which 10 deaths (6.2%) occurred on treatment or 
within 30 days of treatment discontinuation. On-treatment deaths were due to cardiac failure, 
disease progression, general physical health deterioration, sepsis, tuberculosis, subdural 
hematoma, subdural hemorrhage, myeloproliferative disorder, and respiratory failure.
Adverse Events of Interest
Hemorrhage AEs of special interest (AESIs) were reported in 56 patients (34.8%), of which the 
incidence was higher in the 200-mg pacritinib BID group (42.6%) compared with the other 
treatment groups (100-mg pacritinib BID: 25.5%; 100-mg pacritinib QD: 36.5%). The most 
common hemorrhage AESI was epistaxis (10.6% overall). Most of the hemorrhage events (37 of 
56; 66.1%) were reported within the first eight weeks of treatment. Overall, grade 3 or 4 treatment-
emergent hemorrhage was reported in seven patients (4.3%): three patients (5.6%) in the 200-
mg pacritinib BID group (GI hemorrhage, epistaxis, and hematoma), no patients in the 100-mg 
pacritinib BID group, and four patients (7.7%) in the 100-mg pacritinib QD group (muscle 
hemorrhage, epistaxis, and two events of hematuria). Two grade 5 bleeding events were reported, 


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one in the 200-mg pacritinib BID group (subdural hematoma/injury) and one in the 100-mg 
pacritinib BID group (subdural hemorrhage/injury). Study drug was discontinued for three patients
due to hemorrhage events (subdural hemorrhage, hematoma, and one patient with both epistaxis 
and hematuria). The study drug was interrupted for two patients due to hemorrhage events 
(epistaxis and mouth hemorrhage). All other patients with bleeding events continued treatment 
without any dose reduction or interruption.
Cardiac AESIs were reported in 45 patients (28.0%) and the incidence was higher in the 200-mg
pacritinib BID group (40.7%) compared with the other treatment groups (100-mg pacritinib BID: 
21.8%;100-mg pacritinib QD: 21.2%). The most common cardiac AESI was peripheral edema 
(13.0% overall). Most of the cardiac events (27 of 45; 60.0%) were reported within the first eight
weeks of treatment. Overall, grade 3 or 4 treatment-emergent cardiac events were reported in 
nine patients (5.6%): two patients (3.7%) in the 200-mg pacritinib BID group (supraventricular 
arrhythmia, cardiac failure, and peripheral edema),4 patients (7.3%) in the 100-mg pacritinib BID 
group (splenic infarction, cardiac failure, and two events of ejection fraction decreased), and three
patients (5.8%) in the 100-mg pacritinib QD group (syncope and two events of ejection fraction 
decreased). One grade 5 cardiac failure was reported for a patient in the 100-mg pacritinib BID 
group. 
The mean change in the QT interval corrected by the Fridericia method (QTcF) from baseline 
across the treatment groups was approximately 10 ms and no patient had QTcF >500 ms at any 
time point. No patients had left ventricular ejection fraction (LVEF) <20%. Overall,15 % had 
with the incidence being highest in the 100-mg pacritinib BID group (12.7%) 
compared with the other treatment groups (200-mg pacritinib BID: 9.3%; 100-mg pacritinib 
QD:5.8%). Overall, the median worst LVEF change post-baseline ranged from 2.0% to 2.5% 
across the treatment groups.
PAC203 Phase 2 Benefit/Risk Conclusion
Administration of 200-mg pacritinib BID was generally well tolerated. The most common
treatment-emergent non-hematologic AEs were GI, including diarrhea and nausea, which were 
distributed similarly across treatment arms. The most common hematologic AEs were 
thrombocytopenia and anemia, both occurring at higher frequencies in the 200-mg pacritinib BID 
group, however, this did not lead to higher rates of grade 3/4 hemorrhage at higher doses. 
The benefit/risk profile of 200-mg pacritinib BID supports continued investigation of this dose in 
the Phase 3 PACIFICA study comparing pacritinib with physician’s choice (P/C) therapy for 
patients with MF and severe thrombocytopenia.
1.5.5 Rationale for Dosage Selection
The early clinical development program for pacritinib consisted of two-phase 1/2 dose-escalation 
studies (Studies 001 and 003) spanning a dose range of 100 to 600 mg QD in patients with 
advanced myeloid malignancies and chronic idiopathic MF. The maximum-tolerated dose in both 
studies was determined to be 500 mg QD. Based on favorable observations from both studies, 
the 400-mg QD dose level was advanced into the first phase 3 (PERSIST-1) clinical study in 
patients with MF. The most common AE observed in phase 1, phase 2, and PERSIST-1 was 
diarrhea, which was effectively managed with administration of anti-diarrheal agents and/or study 
drug 
interruption 
or 
dose 
reduction.


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Population pharmacokinetic (PPK) analysis suggested that a higher steady-state and daily 
exposure to pacritinib could be achieved by dividing the 400-mg QD dose into a 200-mg BID 
dosing regimen. Informed by these results, the second phase 3 (PERSIST-2) study evaluated the 
efficacy and safety of a 200-mg BID regimen as well as the 400-mg QD regimen. Observationally, 
the results of PERSIST 2 demonstrated that the 200-mg BID regimen showed better efficacy 
relative to BAT for both SVR and TSS as compared to the 400 mg QD regimen.
To identify an optimal dosage of pacritinib for further clinical development in MF, a phase 2
dose-ranging study (PAC203) was initiated, and enrollment was completed in January 2019. 
Three dosage levels (100 mg QD, 100 mg BID, and 200 mg BID) were selected to allow adequate
characterization of dose-response relationships for the efficacy and safety of pacritinib. PPK and 
exposure-response analysis utilizing clinical PK/PD data from all completed clinical studies along 
with data from 54 patients and 109 patients from Week 24 and Week 12, respectively, in the
PAC203 study showed that systemic exposure (area under the curve [AUC], Cmax, and minimum
concentration observed [Cmin]) of the 100-mg QD and 100-mg BID regimens is, as originally 
predicted, well below that of the 400-mg QD and 200-mg BID regimens. Simulation results 
indicate that AUC and Cmin are similar between 200 mg BID and 400 mg QD while the median 
peak concentration (Cmax) is higher with 200 mg QD; however, there is considerable overlap.
Pacritinib exposure and the occurrence of the most common AEs of interest (diarrhea, vomiting, 
nausea, thrombocytopenia, hemorrhage, anemia, and cardiovascular events) were evaluated 
using clinical data from PERSIST-1, PERSIST-2, and the interim data from PAC203. The 
exposure-safety analysis showed no correlation between pacritinib exposure and the occurrence 
of the most common AEs of interest except for GI AEs (including diarrhea, vomiting, and nausea) 
and cardiovascular (CV) AEs. The model predicted the probability of GI AEs for the 200-mg BID 
dose was approximately 14% and approximately 7% for CV AEs.
Taken together, the exposure-efficacy and exposure-safety analyses based on the PERSIST 
studies and the safety and efficacy observations from the PAC203 Phase 2 study indicate that 
the 200 mg BID is an appropriate dose for investigation in a phase 3 study.
2 HYPOTHESIS, OBJECTIVES, AND ENDPOINTS
Jak2-Stat5 signaling pathway sustains the expression of androgen receptor (AR) and AR variants 
(AR-Vs) in PC cells. Inhibition of Jak2-Stat5 signaling depletes expression of AR and AR-Vs in 
PC cell lines, in xenograft tumors grown in nude mice and in patient-derived clinical PCs grown 
in tumor explant cultures ex vivo. We hypothesize that pacritinib through inhibition of the JAK2-
STAT 5 signaling pathway would induce biochemical responses in men with systemic PC by 
depleting expression of AR and AR-V.
2.1 Primary Objectives
To establish the effect of pacritinib on the time to PSA progression in patients with 
biochemical relapse of prostate cancer by assessing the length of time that a given subject 
will be alive and free from PSA progression.


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2.2 Secondary Objectives
1.
To evaluate the absolute PSA nadir as a result of treatment which is expressed for each 
subject in the absolute value and as a percentage, change from baseline.
2.
To determine the time to PSA nadir from the start of treatment. which is the lowest PSA 
on treatment.
3.
To determine the time to next subsequent antineoplastic therapy.
4.
To determine the effect of investigational treatment on testosterone levels which is 
assessed by the change of testosterone from baseline to cycle 4.
5.
To determine the safety and toxicities of the study drug as assessed by CTCAE version 
5.
2.3 Exploratory Objectives
1.
To determine if the study drug affects comprehensive geriatric assessment domains. 
2.
To determine if the study drug combination affects the quality of life. 
3.
To evaluate if positive status for Stat5 activation in the paraffin-embedded tissue sections 
of the diagnostic biopsies
has a trend to predict biochemical response to pacritinib 
treatment. 
2.4 Primary Endpoint
Six-month PSA-progression free survival 
2.5 Secondary Endpoint(s)
1.
Absolute PSA nadir.
2.
Time to PSA nadir.
3.
Time to next subsequent antineoplastic therapy.
4.
Effect of investigational treatment on testosterone levels.
5.
Safety and toxicities of the study drug.
2.6 Exploratory Endpoints 
1.
Effect of pacritinib on CGA domains.
2.
Effect of pacritinib on FACT-P score.
3.
Effect of levels of Stat5 transcription factors in prostate cancer cells determined by 
fluorescence-based immunohistochemistry on biochemical responses response to 
pacritinib.
4.
Identify biomarkers of response/resistance.
3 STUDY DESIGN
3.1 General Description
This is a single-arm, open-label phase 2 study to evaluate the role of pacritinib for patients with 
biochemical relapse after definitive treatment for prostate cancer. Patients will receive pacritinib 
200 mg twice daily. To be eligible, patients are not allowed to have been treated with a JAK2 


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inhibitor. Assigned treatment will continue until the patient experiences progressive disease or 
intolerable adverse events (AEs), withdraws consent, initiates new PC-directed therapy, or the 
study is terminated. In addition to the above, patients will be considered to have discontinued 
treatment if pacritinib is held for >28 consecutive days due to treatment toxicity, or if treatment is 
discontinued for lack of efficacy, or at the request of the principal investigator or the patient. This 
study will be monitored by an Independent Data Monitoring Committee (IDMC).  
3.2 Study Completion
The study will reach study completion approximately 36 months from the time the study opens 
to accrual.
4 SUBJECT PARTICIPATION, DISCONTINUATION, AND 
WITHDRAWAL 
Investigators must follow all MCW IRB requirements and policies regarding subject participation, 
found here:
https://www.mcw.edu/HRPP/Policies-Procedures.htm
4.1 Subject Status
Subject statuses throughout the trial are defined as follows:  
Prescreening: preconsent (subject considering trial or study staff considering a patient 
for the trial per institutional recruitment methods).
Screening: the period after the consent, but prior to eligibility confirmation.
Consented: consented, prior to eligibility confirmation.
Eligible: the local investigator confirms all eligibility criteria apply.
On study/enrolled: date eligibility is confirmed.
On arm: date of enrollment.
On treatment: first-day treatment was given to the last day treatment was given.
Off treatment: the last day treatment was given.
On follow-up: from the last day of treatment to the end of the follow-up period.
Off study: follow-up period completed, with no additional data gathered.
Withdrawn: subject fully withdraws consent (i.e., refuses ALL follow-up, even survival) or 
is taken off the study by the local principal investigator.
4.2 Prescreening and Screening Log
The MCW study principal investigator regularly reviews screen failure reasons to understand 
barriers to accrual and consider amending eligibility criteria. Screen failures are defined as 
participants who were considered for the trial to participate in the clinical trial with or without 
consent but are not subsequently assigned to the study intervention or enrolled in the study.
MCWCC CTO will follow its SOPs regarding prescreening and screening tracking.


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4.3 Consent 
Investigators or their appropriate designees will identify potentially eligible subjects from their 
clinics, subject self-referrals, referrals from other clinicians, and/or other IRB-approved 
recruitment methods. No study conduct, including subject prescreening, can occur until after IRB 
approval.
A written signed informed consent form (ICF) and a Health Insurance Portability and 
Accountability Act (HIPAA)
authorization must be obtained before any study-specific 
assessments are initiated. A signed ICF copy will be given to the subject and a copy will be filed 
in the medical record (per local IRB policies and SOPs). The original will be kept on file with the
study records. 
4.4 Screening Procedures
Refer to the study calendar of events.
Visit procedures that were performed as standard of care before consent (without the specific 
intent to make the subject eligible for the trial), may count toward screening tests and eligibility if 
they are within the screening window. 
4.5 Biospecimen studies and procedures 
Archived tissue samples will be requested and are required if available. Tumor and blood 
biomarkers to be evaluated to support the exploratory objectives of the study may be evaluated 
per study calendar. Biomarker assessments that may have the potential to identify patients 
likely to respond to treatment with investigational agents will be investigated to determine a 
patient’s biomarker status and for possible correlation with efficacy endpoints.
All samples collected for biomarker analyses will be stored and analyzed at Dr. Nevalainen’s 
and Dr. Rui’s laboratory and may be used for subsequent research relevant to evaluating 
biological and/or clinical response to pacritinib.
Quantitative fluorescence-based immunohistochemistry will be used to determine levels of 
nuclear localized Stat5 in prostate cancer cells, to provide pilot data to explore the hypothesis 
that high levels of nuclear localized Stat5 in cancer cells prior to Jak2-inhibitor treatment 
correlate with responsiveness to pacritinib treatment.  
Specimens to be provided:
One H&E and five unstained sections from formalin-fixed, paraffin-embedded prostate cancer 
samples from before initiation of pacritinib treatment (biopsy or resected specimen) will be 
required if available. Surgical specimens would be preferred over biopsy specimens when 
available. All archived tissue samples available may be used, not just the most recent sample.
Blood (2x10ml EDTA tube) will be collected per calendar and processed as below. Plasma will 
be isolated for cell-free DNA extraction and exosome isolation. The cell-free DNA will be tested 
for genetic and epigenetic changes. The exosomes will be tested to quantify their microRNA 
contents. Correlative analyses will be performed to associate the genetic and epigenetic 


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changes with treatment responses. These analyses will include (but not limited to) Cox 
regression, Kaplan-Meir and area under the curve (AUC)
Blood will be stored in Dr. Nevalainen’s laboratory. If a response is detected after the first 10 
patients, a protocol amendment will occur to allow for analysis of blood specimens. .Tissue and 
blood will be sent to: 
Marja Nevalainen’s laboratory,
TBRC C4960, Medical College of Wisconsin, 
8701 Watertown Plank Road, Milwaukee, WI 53226
(office 414-955-2103, mobile 301-219-6689; mnevalainen@mcw.edu)
Laboratory staff:
Vindhya Udhane, PhD (Research Scientist; 414-955-2938; mobile: 234-706-8384; 
vudhane@mcw.edu)); 
Cristina Maranto PhD (Research Scientist; office 414-955-2115; mobile 414-897-6211;
cmaranto@mcw.edu) 
Either Dr. Nevalainen or laboratory staff can be contacted for any questions regarding specimen
(tissue and blood) handling.
1.
Biomarkers to be assessed include Signal Transducer and Activator of Transcription-
5a/b (Stat5a/b) and will be correlated with response to treatment. 
2.
If adequate tissue is not available for all study biomarkers to be done, the patient would 
still qualify and be enrolled to the study.  
Pathologic Evaluation and Handling of Tissue Specimens:
1.
Tissue for analysis will be subject to routine pathological analysis. Routine hematoxylin 
and eosin (H&E) stain will be used for morphological analysis and for the determination of 
carcinoma diagnosis. The samples will be assessed by our GU pathologists. 
2.
One H&E slide and five unstained slides will be reserved for study labs/biomarkers and 
will be sent to Dr. Marja Nevalainen’s laboratory (suite C4960) at the Medical College of 
Wisconsin Translational and Biomedical Research Center (TBRC).
3.
Cancer cell levels of Stat5a/b protein will be quantified on slides, using optimized 
fluorescence-based multiplexed immunohistochemical protocols.
Handling of Blood Specimens 
1.
Collect blood in 2x10ml K2EDTA venous blood collection tubes.
2.
Gently invert sample(s) eight to 10 times and process within 30 minutes, but no longer 
than two hours after blood draw.  
3.
Centrifuge specimens at approximately 3000 rpm in a standard clinical centrifuge for 10 
minutes at RT.
4.
Being careful to not disturb the buffy coat, transfer the platelets-rich plasma to a 15-ml 
conical tube and spin again at 3000 rpm to separate platelets from platelets-poor plasma.
5.
Transfer buffy coat layer into a 2-ml cryovial tube. Some red blood cell contamination is 
expected.
6.
Once finished with the second spin, transfer platelets-poor plasma to 1-ml cryovial tubes, 
being careful not to disturb pellet. 


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7.
Label all aliquots with study, patient ID, date/time of collection, timepoint, and specimen 
(i.e. PPP – platelet poor plasma, BC – buffy coat, PL - platelet).  
8.
Immediately freeze samples at -80°C.


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4.5 Eligibility Confirmation
Study staff must adhere to MCWCC CTO SOPs regarding eligibility review/confirmation. 
No waivers of protocol eligibility will be granted. When clinical factors relating to an eligibility item 
are unclear or questionable, the MCW PI can only provide guidance or clarification on eligibility.
Any eligibility questions should be directed to Dr. Kilari at dkilari@mcw.edu.
Inclusion Criteria
1.
2.
Histologically or cytologically confirmed prostate adenocarcinoma.
3.
Prior radical prostatectomy or definitive radiation.
4.
9 months at the time of 
study 
entry( 
calculated 
per 
MSKCC 
prostate 
nomogram:
https://www.mskcc.org/nomograms/prostate/psa_doubling_time). Calculation of PSA 
doubling time should include the use of all available PSA values obtained within the past 
12 months prior to randomization, with a minimum of three values separated by at least 
two
0.1 ng/mL and should be measured in the same laboratory whenever feasible. 
5.
Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical 
assessment of disease characteristics and patient comorbidities. (N/A for patients who 
underwent definitive radiation therapy).
6.
Screening PSA > 0.5 ng/mL.
7.
No definitive evidence of metastases on screening imaging per the judgment of the 
investigator. Pelvic lymph nodes measuring 1.5 cm or less in short axis diameter are 
allowed. Lesions identified on imaging modalities (e.g. PSMA or choline PET) that are not 
visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on 
bone scan should be followed up with additional imaging as clinically indicated.
8.
Screening serum testosterone > 50 ng/dL.
9.
Eastern Cooperative Oncology Group (ECOG), Performance Status grade 0-1 or 
70.
10. No prior JAK2 inhibitor treatment.
11. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one 
of the following:
Practice effective barrier contraception and another effective method of birth control if 
he is having sex with a woman of childbearing potential during the entire study period 
and through 90 calendar days after the last dose of study agent
12. Ability to understand a written informed consent document, and the willingness to sign it.
13. Left ventricular cardiac ejection fraction of
50% by echocardiogram or multigated 
acquisition (MUGA) scan.
14. Willing to provide blood and tissue for research analysis. (encouraged but not necessary 
for inclusion in trial).
15. Adequate organ function as defined by the following laboratory values at screening:
o
Serum aspartate transaminase (AST), serum glutamic oxaloacetic transaminase 
[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic 
transaminase [SGPT]) < 2.5 x upper limit of normal (ULN).
o
bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin 
the subject may be eligible).


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o
-screening is allowed.
o
Estimated GFR > 45 ml/min using Cockroft-Gault equation.
o
three months prior to randomization.
o
Hemoglob
three months prior to randomization.
o
.
o
o
Adequate coagulation defined by prothrombin time (PT)/international normalized 
ratio (INR) and
.
Exclusion Criteria
A potential subject who meets any of the following exclusion criteria is ineligible to participate in 
the study.
1.
Previously treated with pacritinib.
2.
Prior systemic treatment with androgen deprivation therapy and/or first-generation anti-
androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate 
cancer. Prior ADT and/or first-generation anti-androgen in the (neo)adjuvant, definitive 
and/or salvage setting in conjunction with radiation or surgery is allowed provided last 
effective dose of ADT and/or first-generation anti-androgen is 
12 months prior to the 
date of randomization and the 
3.
Prior treatment with CYP17 inhibitor (e.g., ketoconazole, abiraterone acetate, galeterone) 
or next-generation androgen receptor antagonist including apalutamide or enzalutamide.
4.
Prior chemotherapy for prostate cancer
5.
Use of 5-alpha reductase inhibitor within 42 days prior to randomization.
6.
Use of investigational agents within 28 days prior to randomization.
7.
Use of other prohibited medications within seven days prior to Cycle 1 Day 1 on study 
(see Appendix 3 and 4 for list of prohibited medications).
8. Systemic treatment with a strong CYP3A4 inhibitor or a strong CYP450 inducer within 14 
days prior to treatment Day 1 (Appendix 3 and Appendix 4, respectively)
9. Prior bilateral orchiectomy.
10. Uncontrolled hypertension.
11. Baseline severe hepatic impairment (Child-Pugh Class B & C).
12. An intercurrent illness that is not controlled, such as active infection, psychiatric 
illness/social situations that would limit compliance with study requirements.
13. Any chronic medical condition requiring a higher dose of corticosteroid than an equivalent 
of 10 mg prednisone/prednisolone per day.
14. Significant recent bleeding history, as defined a
2 within three months 
prior to treatment Day 1, unless precipitated by an inciting event (e.g., surgery, trauma, or 
injury)
15. Systemic treatment with medications that increase the risk of bleeding, including 
anticoagulants (warfarin, direct oral anticoagulant, etc.), antiplatelet agents (except for 
, vascular endothelial growth factor (anti-VEGF) agents, 
and daily use of COX-1 inhibiting nonsteroidal anti-inflammatory agents (NSAIDs) within 
14 days prior to treatment Day 1.
16. Systemic treatment with medications that can prolong the QT interval within 14 days prior 
to treatment Day 1. Shorter washout periods may be permitted with the approval of the PI, 
provided that the washout period is at least five half-lives of the drug prior to treatment
Day 1.
17.
cardiac conditions within six months before


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treatment Day 1. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular
conditions may be considered for inclusion, with the approval of the PI, if stable and 
unlikely to affect patient safety.
18. QT corrected by the Fridericia method (QTcF) prolongation >450 ms or other factors that
increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as 
serum potassium <3.0 mEq/L that is persistent and refractory to correction]), or history of 
long QT interval syndrome.
19. New York Heart Association Class II, III, or IV congestive heart failure (Appendix 7).
20. Any active GI or metabolic condition that could interfere with absorption of oral medication.
21. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn’s
disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation.
22. Other malignancy within three years prior to treatment Day 1, other than curatively treated 
basal cell or squamous cell skin or corneal cancer; curatively treated carcinoma in situ of 
the cervix; or in situ breast carcinoma after complete surgical resection.
23. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, 
psychiatric illness, or social situation that, in the judgment of the treating physician, would 
limit compliance with study requirements.
24. Known seropositivity for human immunodeficiency virus.
25. Known active hepatitis A, B, or C virus infection.
I have reviewed all inclusion and exclusion criteria and confirm the subject is eligible.”
_______________________________________        
_______________
                   (CRC Signature)                                                     
        (Date)
_____________________________________        
_______________
(Investigator/Enrolling Physician Signature)                                     (Date)


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4.6 Discontinuation of Study Treatment, Withdrawal, and Compliance
Treatment duration is 2 years. Patients may continue drug beyond two years if, in the opinion of 
the treating physician, the patient is benefitting from treatment and benefits outweigh any risks 
of therapy
Discontinuation from the study treatment does not mean discontinuation from the study. The 
subject will be considered in follow-up, study procedures should still be completed as indicated 
by the study protocol, and AEs/SAEs will continue to be reported according to this protocol.
In the absence of treatment delays due to adverse events, study treatment/intervention may 
continue until: 
Disease progression per PCWG3 guidelines 
General or specific changes in the subject’s condition renders the subject unacceptable 
for further treatment in the investigator’s judgment. 
An inter-current illness that prevents further treatment administration. 
The subject decides to withdraw from the study. 
The subject has significant noncompliance with the protocol (see below).  
Unacceptable adverse event(s) and/or dose level reduction beyond requirements as 
detailed in this protocol. 
The clinical need for concomitant therapy that is not permitted in the study.
Subjects who sign the informed consent form, enroll and receive the study intervention, 
but subsequently withdraw, or are withdrawn or discontinued from the study will not be 
replaced. 
Progression of disease 
Progression of disease per PCWG3 is defined as one or more of the following:
PSA progression
drug. Monitor PSA by cycle but plan to continue through early rises for a minimum of 12 weeks 
unless other evidence of progression.
If there is a decline in PSA from baseline: record time from baseline to the first PSA increase 
weeks later (i.e., a confirmed rising trend).
If there is no decline in PSA from baseline but stable PSA at 12 weeks: PSA progression will be 
defined  as 
25% and 
2 ng/mL from PSA at 12 weeks .
Radiographic progression
Radiographic progression will be assessed per RECIST 1.1. Any new unequivocal bone lesion 
is considered progression, except if that lesion appears in the first post-treatment scan; in that 


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case, document the event, continue treatment until two additional new lesions appear, and 
record both events.
Consent Withdrawal
A subject may decide to withdraw from the study at any time. MCWCC CTO will follow their IRB
of record’s SOPs regarding consent withdrawal.
If a subject intends on withdrawing consent, staff should confirm which of the following options 
the subject chooses and document the discussion:
Full consent withdrawal, with no study follow-up.
Selective consent withdrawal from the interventional portion of the study but agree to 
continued follow-up of associated clinical outcome information.        
Investigator-initiated Withdrawal
The investigator will withdraw a subject whenever continued participation is no longer in the 
subject’s best interests. Reasons for withdrawing a subject include, but are not limited to, disease 
progression, the occurrence of an adverse event or a concurrent illness, a subject’s request to 
end participation, a subject’s noncompliance, or simply significant uncertainty on the part of the 
investigator that continued participation is prudent. The reason for study withdrawal and the date 
the subject was removed from the study must be documented.
4.7 Lost to Follow-up
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit and/or is unable to be reached for follow-up:
The investigator or designee must make every effort to regain contact and/or reschedule a 
missed visit with the participant.
A participant is deemed lost to follow-up if his/her status cannot be obtained after all of the 
following occurs at two consecutive scheduled protocol calendar timepoints:
o
Three telephone calls (at least one day apart) from the study team are unanswered,
                  AND 
o
A letter (Appendix 2) to the participant’s last known mailing address goes unanswered,
AND
o
These contact attempts must be documented in the participant’s medical record or 
study file.
Update OnCore® (Follow-up tab and eCRF) when a participant is officially considered lost to 
follow-up.
If a subject is considered lost to follow-up, but subsequently contacts the study team, the 
subject should be considered in follow-up again.
4.8 Accrual Suspension and Closure
The MCW PI facilitates the suspension and closing of accrual in the following manner:
OnCore® tracks accrual throughout the study.


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If the study must be suspended, OnCore® is updated to ‘suspended’ status.
When the accrual number is reached, OnCore® notifies staff of study closure.
4.9 End of Study Definition
A participant is considered to have completed the study if he or she completed all phases of the 
study, including the last visit or the last scheduled procedure shown in the calendar of events or 
has been discontinued.
4.10 Study Discontinuation and Closure
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause (as determined by the MCW study PI, DSMC, sponsor, and/or IRB). Written 
notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to study participants, investigator, funding agency, the 
Investigational New Drug (IND) sponsor, and regulatory authorities. If the study is prematurely 
terminated or suspended, the MCW principal investigator (PI) will promptly inform the MCW 
Institutional Review Board (IRB), and the sponsor and will provide the reason(s) for the 
termination or suspension. Study participants will be contacted, as applicable, and be informed 
of changes.
5 TREATMENT PLAN
5.1 Pacritinib 
5.1.1 Study Treatment Description and Storage
Pacritinib for oral administration is supplied in capsules containing 100 mg (as the free base) in 
red cap/gray body size 0 opaque hard gelatin capsules. The inactive ingredients are 
microcrystalline cellulose, magnesium stearate, and polyethylene glycol 8000.
Each capsule contains 146-mg of pacritinib citrate, which is equivalent to 100-mg pacritinib free 
base. Pacritinib capsules should not be opened or crushed. Direct contact of the powder in 
pacritinib capsules with the skin or mucous membranes should be avoided. If such contact occurs, 
affected areas should be washed thoroughly with water. Pacritinib capsules should be stored at 
controlled room temperature 20°C to 25°C or 68°F to 77°F, with excursions allowed from 15°C to 
30°C or 59°F to 86°F. All pacritinib supplies must be kept in a restricted-access area.
5.1.2 Dosage, Route, and Mode of Administration
Patients assigned to pacritinib will be supplied with 100-mg capsules of pacritinib. Patients will 
take two 100-mg capsules of pacritinib BID, orally, at the same time of day, with or without food. 
On days when ECGs are to be obtained, pacritinib will be administered in the clinic to facilitate 
the performance of predose assessments. Any missed or vomited doses should not be retaken 
or replaced.


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Regimen Description
Study 
agent
Route
Premedication; 
precautions
Dose
Duration
Pacritinib
Oral
None
200 mg
b.i.d
Continue 
treatment 
until 
progression of disease (at least 
12 
weeks) 
or 
meeting 
discontinuation criteria.
5.2 Dose Adjustment
5.2.1 Treatment Interruption and Discontinuation 
Safety parameters including AEs, hematology, and serum chemistry will be monitored according 
to the protocol. Pacritinib treatment may be withheld for up to four weeks due to drug-related 
toxicities. A longer recovery period may be allowed based on the toxicity but must be agreed upon 
between the investigator and study PI.
Pacritinib should be withheld seven days prior to planned invasive procedures and concurrently 
with any unplanned invasive procedure. Pacritinib may be restarted after two days without active 
signs or symptoms of active bleeding. Pacritinib dosage may also be held at the discretion of the 
investigator. The PI must be notified of such dose holds. After treatment interruption, patients may 
resume pacritinib treatment per the dose management guidelines below.
After treatment interruption, patients may resume the pacritinib treatment at the same dose level 
or at a reduced dose level. No dose re-escalation is allowed.
Pacritinib dose levels for dose adjustments only:
1.
Dose level -1: Pacritinib 100 mg BID
2.
Dose level -2: Pacritinib 100 mg QD
Any 
prompt dose modification, with reduction to 
50% of current pacritinib dose.
Additional drug discontinuation criteria include any treatment-related 
•Grade 3 nausea/vomiting or diarrhea that resolves within 72 hours with supportive care
•Grade 3 fatigue that lasts more than 1 week 
•Grade 3 electrolyte abnormality that is asymptomatic and resolves within 72 hours.
Study can be terminated early for multiple reasons including. 


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1.
Poor adherence to protocol and regulatory requirements 
2.
Incidence or severity of adverse drug reaction in this or other studies indicates a potential 
health hazard to subjects 
3.
Plans to modify or discontinue the development of the study drug. 
4.
Events that meet Hy’s law criteria 
Should the study be terminated at the interim analysis due to futility, patients with ongoing 
responses will be allowed to continue with treatment at the discretion of PI and CTI BioPharma.
5.2.2 Dosage Management Guidelines for Hematologic Toxicity and Related
Complications
Hematology parameters, including CBC, differential, will be evaluated at regular intervals during 
the study. These parameters should be monitored more frequently if clinically required. 
Unscheduled local laboratory test results may be used for the assessment and management of 
patients in real-time. 
Table 1 indicates the required dose interruptions and modifications for hematologic toxicities and 
complications such as hemorrhage and febrile neutropenia that are treatment related . Of note, if 
more than one toxicity is experienced simultaneously, the higher-grade toxicity should determine 
the dose interruption/modification. Treatment-related toxicities are those that are considered at 
least possibly related to study drug.
Table 1. Treatment Toxicity and Dosage Management: Hematologic Toxicities and Related 
Complications
Event
CTCAE Grade
Management/Action
Thrombocytopenia 
For patients starting 
treatment with
baseline (Day 1) grade 
1 thrombocytopenia 
who have treatment-
related
1
grade decrease in 
platelets 
Hold pacritinib for up to 10 days 
until recovery of platelet count to 
recovery, restart at 50% of the prior 
dose. If thrombocytopenia recurs at 
the 100 mg BID dose level, 
discontinue pacritinib.
Hemorrhage 
Treatment-emergent 
hemorrhage Grade 2
Hold pacritinib for up to seven days 
until hemorrhage resolves. Restart 
with a 50% dose reduction. If event 
recurs, discontinue pacritinib
Grade 3 
Discontinue pacritinib.
Grade 4 
Discontinue pacritinib.
Neutropenic
infections, 
including neutropenic sepsis 
Grade 2
Hold pacritinib for up to seven days 
and start at 50% of the dose once 


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resolved (100 mg BID). If toxicity 
recurs discontinue pacritinib 
Grade 3
Discontinue pacritinib
Grade 4 
Discontinue pacritinib
Coagulation Testing 
Coagulation testing will include PT, INR, PTT, at screening. Additional coagulation testing should 
be done as clinically indicated. 
These results will be taken into account, together with baseline platelet counts and prior medical 
history of bleeding, to help guide ongoing hematologic monitoring of platelet counts and clinical 
monitoring for bleeding. Pacritinib dosage modifications will be implemented for clinically 
significant AEs identified with this testing per the guidelines in Table 5.
5.2.3 Pacritinib Dosage Management Guidelines for QTc Interval Prolongation, Reduction 
in Ejection Fraction, and Other Cardiac Toxicities
A 12-lead ECG (collected in triplicate), including QTcF calculation, will be performed during 
Screening and at Cycle 1 Day 1,, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, and every four
months thereafter provided there is normal QTcF.
Treatment should be modified as shown in Table 2, as recommended by the FDA in case of QTcF 
interval prolongation. Dose levels referenced in the following tables refer to the following available 
doses: 200 mg BID, 100 mg BID, and 100 mg QD.
Table 2. Pacritinib-Related QTc Prolongation, Clinically Significant Decreases in Cardiac Ejection 
Fraction and Other Cardiac Toxicities
CTCAE v5 Toxicity Grade
Management/Action
1
No change. 
2 (First occurrence) 
For patients with grade 2 LVEF 
decreased at baseline (LVEF 45%-
50%) and further decreases in LVEF 
on the study, see Table 3)
Hold pacritinib. 
14
days, treatment may be resumed at the next 
lower dosage level (or discontinued, if toxicity 
occurred while taking 100 mg QD). 
within 
14
days 
requires 
treatment 
discontinuation. 
2 (second occurrence) 
Discontinue treatment. 
3
Discontinue treatment. 
4
Discontinue treatment. 


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Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; LVEF = left ventricular ejection 
fraction; QD = once daily; QTc = corrected QT interval.
A transthoracic echocardiogram will be performed at screening, Cycle 2 Day 1, Cycle 5 Day 1,
Cycle 8 Day 1, and every six months thereafter provided there is normal LVEF and no clinical 
evidence of heart failure. The window for all TTEs is -14 days from Day 1 of the cycle it is due at.
Pacritinib dosage modifications will be implemented for clinically significant cardiac ejection 
fraction changes as per Table 2 and Table 3.
For patients with a grade 2 decreased cardiac ejection fraction at baseline (left ventricular ejection
fraction [LVEF]=50% Table 3 should be used for any further decreases in LVEF.
If pacritinib treatment is resumed after holding for ejection fraction abnormality, ejection fraction 
should be reassessed approximately seven days later, then again within 12 weeks following the 
seven-day reassessment. If stable, ejection fraction will be checked every six months during the 
follow-up period and at the End of Treatment Visit. Additional ejection fraction testing shall be 
done as clinically indicated.
Table 3. Pacritinib-related Clinically Significant Decreased Cardiac Ejection Fraction 
for Patients with Grade 2 Ejection Fraction (LVEF 45%-50%) at Baseline
CTCAE v5 Toxicity Grade
Management/Action
Worsening of grade 2; 10-
19% drop from bassline 
Hold pacritinib for one to two weeks and reassess LVEF. If 
LVEF returns to baseline, the patient may resume treatment at 
the next lower dose level; if does not resolve, pacritinib should 
be discontinued.
3
.
Discontinue treatment.
4
Discontinue treatment. 
In patients who resume pacritinib treatment after holding treatment for grade 2 QTc interval 
prolongation, follow-up ECGs (in triplicate) are recommended on Days 1, 7, 14, 28, and 56 after 
pacritinib restart. After the restart of pacritinib, QTc monitoring should follow this schedule with 
ECGs obtained in triplicate: 
Restart Day 1 at four hours (± one hour) after ingestion of the first reduced dosage 
Restart Day 7 (± two days) four hours after dosing (± one hour) 
Restart Day 14 (± two days) four hours after dosing (± one hour) 
Restart Day 28 (± two days) at any time relative to dosing 
Restart Day 56 (± seven days) at any time relative to dosing 
seven days, discontinue all treatment with 
pacritinib. If grade 2 toxicity recurs despite dosage reduction discontinue all treatment with 
pacritinib. For grade 3 and 4 QTc prolongation, discontinue all treatment with pacritinib. 


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Other Cardiac Toxicities 
Discontinue treatment with pacritinib for all other grade 3 and 4 cardiac toxicities. 
5.2.4 Pacritinib Dosage Management Guidelines for Diarrhea
The need for managing GI effects of pacritinib, particularly diarrhea, should be anticipated. A 
careful baseline evaluation of bowel habits (frequency and consistency of bowel movements) 
should be obtained at baseline for all patients. At the baseline visit, all patients in the pacritinib 
arm will be provided with a prescription (and instructions to fill that prescription) for loperamide 
(Imodium®) or a similarly effective antidiarrheal drug. Patients will be instructed to start taking the 
prescribed loperamide or other antidiarrheal drugs per package and physician instructions as 
soon as they notice any changes in frequency or consistency of bowel movements after starting 
study treatment. Early intervention for diarrhea should be initiated for patients in the pacritinib arm 
with increases of one grade or more in diarrhea (Appendix 7). At the investigator’s discretion, 
prophylactic use of antidiarrheals may be initiated for patients or populations in whom it is judged 
necessary to enhance patient safety. Standard supportive care measures to control symptoms of 
GI toxicity such as diarrhea, constipation, and nausea should be provided.
Treatment with antidiarrheals is advised for all patients who experience new-onset diarrhea (Table 
4). Dose modifications for patients with diarrhea, nausea, and vomiting that is considered at least 
possibly related to study drug are described in Table 4.
Table 4. Treatment Toxicity and Dosage Management for drug-related Diarrhea, Nausea, 
Vomiting
CTCAE 
v5 
Toxicity Grade
Management/Action
1
No Change
2
Hold pacritinib for up to seven days 
days, treatment will be resumed at the same level
If the toxicity recurs after the restart at the same dosage level, 
treatment may only be resumed at the next lower dosage level start 
at 50% of the dose once resolved (100 mg BID)
3
Hold treatment. 
seven days, treatment may be resumed at the same level or the 
next lower dosage. Concomitant antidiarrheal treatment is required 
for patients restarting pacritinib at the 100 mg QD dosage level. 
If the toxicity recurs after the restart at the same dosage level,
treatment may only be resumed at the next lower dosage level. 
than seven days, treatment may be resumed only at the next lower 
dosage level. Discontinuation is required if on hold from the 100 mg 
QD dosage level. Concomitant antidiarrheal treatment is required 
for patients restarting pacritinib at the 100 mg QD dosage level. 


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CTCAE 
v5 
Toxicity Grade
Management/Action
If the toxicity recurs after the restart at the lower dosage level, 
pacritinib treatment must be discontinued. 
4
Discontinue pacritinib
5.2.5 Pacritinib Dosage Management Guidelines for Pacritinib-Related Nonhematologic 
Toxicities Other than QTc Prolongation, Decreased Cardiac Ejection Fraction, Other 
Cardiac Toxicities or Diarrhea
As defined in Table 5, a maximum of two dosage reductions are allowed for pacritinib-related 
nonhematologic toxicities other than QTc prolongation, decreased cardiac ejection fraction, or 
diarrhea.
Table 5. Treatment Toxicity and Dosage Management: Pacritinib-Related Nonhematologic 
Toxicities Other than QTc Prolongation, Decreased Cardiac Ejection Fraction, Other 
Cardiac Toxicities or nausea, vomiting and Diarrhea
CTCAE
v5 
Toxicity Grade
Management/Action
1 or 2
No change. 
3
Hold treatment. 
seven days, treatment may be resumed at the same level or the next 
lower dosage, at the discretion of the investigator after discussion 
with the Sponsor. 
Toxicity that does not resolve to grade <1 or to the baseline grade 
within seven days requires dosage reduction to the next lower 
dosage.
4
Hold treatment. 
If the toxicity resolves to grade <1 or to the baseline grade within 
seven days, treatment may be resumed, but the dosage will be 
reduced by one dosage from the level at which the toxicity was 
observed. 
If grade 4 toxicity occurs at the lowest dosage of 100 mg QD, the 
patient should be discontinued from the study. 
5.3 Concomitant and Excluded Therapies
Patients should receive full supportive care, including transfusions of blood and blood products,
antidiarrheal and antiemetic agents, and antibiotics when appropriate.
Patients may not receive other investigational agents during the study.


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Patients must not receive treatment with any potent CYP3A4 inhibitors for one week prior to the 
administration of pacritinib and during treatment with pacritinib. 
The following therapies and procedures are prohibited for all patients during the washout period 
and throughout the treatment phase of the study.:
Strong CYP3A4 inhibitors (Appendix 3) and strong CYP450 inducers (Appendix 4), 
except as needed to treat AEs, with Medical Monitor approval.
Any drugs with significant potential for QTc prolongation (Appendix 6), except as needed 
to treat AEs, with PI approval.
5.4 Dietary Restrictions
None.
6 ADVERSE EVENTS: DEFINITIONS, COLLECTION AND REPORTING 
REQUIREMENTS
6.1 Definitions
6.1.1 Adverse Event
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship with 
this treatment. (International Conference on Harmonisation [ICH], E2A, E6).
This study will utilize the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0, located on the CTEP web site:
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
AEs may be spontaneously reported by the patient and/or in response to an open question from 
study personnel or revealed by observation, physical examination, or other diagnostic procedures.
6.1.2 Serious Adverse Event (SAE) 
Serious Adverse Event (SAE) means any untoward medical occurrence that results in any of the 
following outcomes:
Death. Results in death.
Life-threatening. Is life-threatening (refers to an AE in which the patient was at risk of 
death at the time of the event. It does not refer to an event which hypothetically might have 
caused death if it were more severe).


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Hospitalization. Requires inpatient hospitalization or prolongation of an existing 
hospitalization.
Disability/incapacity. Results in persistent or significant disability or incapacity. 
(Disability is defined as a substantial disruption of a person’s ability to conduct normal life 
functions).
Pregnancy
Medically important event. This refers to an AE that may not result in death, be 
immediately life-threatening, or require hospitalization, but may be considered serious 
when based on appropriate medical judgment, may jeopardize the patient, require medical 
or surgical intervention to prevent one of the outcomes listed above, or involves suspected 
transmission via a medicinal product of an infectious agent. Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse; any organism, virus, or infectious 
particle (e.g., prion protein transmitting Transmissible Spongiform Encephalopathy), 
pathogenic or nonpathogenic, is considered an infectious agent.
6.1.3 Attribution of an Adverse Event
An assessment of the relationship between the adverse event and the medical intervention, using 
the following categories: 
Definitely Related: The AE is clearly related to the intervention. There is clear evidence to 
suggest a causal relationship, and other possible contributing factors can be ruled out. 
Probably Related: The AE is likely related to the intervention. There is evidence to suggest a 
causal relationship, and the influence of other factors is unlikely. 
Possibly Related: The AE may be related to the intervention. There is some evidence to suggest 
a causal relationship (e.g., the event occurred within a reasonable time after administration of the 
trial medication). However, the influence of other factors may have contributed to the event (e.g.,
the subject’s clinical condition, other concomitant events). 
Unlikely: The AE is doubtfully related to the intervention. A clinical event, including an abnormal 
laboratory test result, whose temporal relationship to drug administration makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time after administration 
of the trial medication) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the subject’s clinical condition, other concomitant treatments). 
Unrelated: The AE is clearly NOT related to the intervention. The AE is completely independent 
of study drug administration, and/or evidence exists that the event is definitely related to another 
etiology. 
6.1.4 Expectedness of an Adverse Event
Study Investigator or treating Physician will be responsible for determining whether an AE is 
expected or unexpected as indicated in the protocol, informed consent form, and/or drug 
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of the event is NOT consistent with the risk information previously described for the study 
intervention.
6.2 Collection and Reporting Requirements for Adverse Events and Serious Adverse  
      Events
6.2.1 Collection of Adverse Events
All (or specify if only certain grade AE needed) adverse events (including SAEs) must be recorded 
in OnCore® and/or an adverse event log. All AEs required to be collected must be graded 
according to the CTCAE v5. When possible, signs and symptoms indicating a common underlying 
pathology should be noted as one comprehensive event. The investigator’s or treating physician’s 
assessment of AE attributions must also be documented. 
AEs will be collected from the time the subject signs the consent form through 30 days post last 
dose of study drug(s). AEs will be tracked and followed until resolution, subject withdraws 
consent, or is lost to follow-up (including subjects who discontinue early). All adverse events 
collected per the protocol will be followed with appropriate medical management until they are 
resolved, if they are related to the study treatment, or until the investigator deems the event to be 
chronic.
Please see section 6.2.2 and table 6 to identify the adverse events that need to be reported. 
6.2.2 Reporting of Adverse Events and Serious Adverse Events
Please refer to table 6 below to identify adverse events that meet reporting requirements. 
All serious adverse events (SAEs) that occur after the subject has signed the consent form 
through 30 days post last dose of study drug(s) will be reported. All SAEs will be followed until 
satisfactory resolution, or until the investigator deems the event to be chronic.
All serious adverse events (SAEs) must also be documented in OnCore®.
SAEs (regardless of attribution) will be reported to CTI within 24 hours after the lead investigator 
learns of the event. 
Attribution
SAE
AE
Grade 1, 2 & 3
Grade 4 and 5
Grade 3
Grade 4 
Expected
Unexpected
Expected
Unexpected
Unexpected
Expected
Unexpected


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Table 6
1.
Guidance on adverse event reporting to the IRB is available online at MCW IRB Policies and 
Procedures.
2.
For expedited DSMC reporting, the study coordinator/research nurse must notify the DSMC 
via email including the subject ID, date of event, grade, relatedness, expectedness, and a 
short narrative. The DSMC will review data entered into OnCore®.
3.
For routine reporting, the events will be reported to IRB as part of the annual continuing 
progress report and the DSMC will review data entered into OnCore® at the time of scheduled 
monitoring.
4.
Fatal or life-threatening SAEs meeting the criteria indicated in the above table will be reported 
to FDA no later than seven calendar days after study staff’s initial awareness of the event. If 
the SAE is not fatal or life-threatening and meets the above criteria, the timeline for submitting 
an IND safety report to FDA is no later than 15 calendar days after study staff’s initial 
awareness of the event. See section 6.2.3 for detailed reporting instructions.
6.2.3 Reporting Instructions 
Food and Drug Administration 
An IND safety report will be submitted for any adverse event that meets all three 
definitions: possibly related to the study drug, unexpected, and serious. If the adverse 
event does not meet one of the above definitions, it should not be submitted as an 
expedited IND safety report. 
Any relevant additional information that pertains to a previously submitted IND safety 
report will be submitted to FDA as a Follow-up IND Safety Report without delay, as soon 
as the information is available (21 CFR 312.32(d)(2)).
Suggested Reporting Form:
Unrelated
Unlikely
IRB1 and 
DSMC2-
Routine 
Review3
CTI 
Biopharma
IRB1 and 
DSMC2-
Routine 
Review3
IRB1-
Routine 
Review3
DSMC2-
Within 5 
calendar 
days
CTI 
Biopharma
IRB1-
Routine 
Review3
DSMC2-
Within 5 
calendar 
days
DSMC2-
Routine 
Review3
DSMC2-
Within 5 
calendar 
days
DSMC2-
Within 5 
calendar 
days
Possible
Probable
Definite
IRB1 and 
DSMC2-
Within 5 
calendar 
days
FDA4
CTI 
Biopharma
IRB1 and 
DSMC2-
Within 5 
calendar 
days
FDA4
CTI 
Biopharma


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US FDA MedWatch 3500A:  
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm
CTI BioPharma
All serious adverse events (SAEs) must also be faxed to CTI BioPharma’s local safety 
representative at 1-866-660-8967 within 24 hours of study staff awareness. The report 
should include deidentified Oncore® SAE report along with MedWatch form. It may also 
be emailed to pv@ctibiopharma.com.
All pacritinib-related non-serious adverse events (any grade) should be reported to CTI at 
the end of the study.
SAEs (regardless of attribution) should be reported to CTI within 24 hours after the lead 
investigator learns of the event.
Sponsor-Investigator shall report investigational drug product quality complaints to CTI 
within 24 hours after the lead investigator learns of the event, or if the event or reporting 
time frame occurs during a weekend or holiday, the quality complaints will be submitted 
to CTI the following business day. This includes any instances wherein the quality or 
performance of a CTI product (marketed or investigational) does not meet expectations 
(e.g., color, odor, appearance, quality, safety, effectiveness, suspected contamination) or 
that the product did not meet the specifications defined in the application for the product 
(e.g., unexpected labeling or contents). The product quality also includes quality of the 
drug delivery device (in this case, the capsule). As such, device defects should be reported 
according to the instructions on the PQC Form provided by CTI. 
6.3 Unanticipated Problem Involving Risk to Subject or Other (UPIRSO)
The investigator and his or her team will follow the Medical College of Wisconsin policies related 
to unanticipated problems involving risks to subjects or others. This information may be found on 
the Human Research Protection Program website.
6.4 Subject Complaints
If a complaint is received by anyone on the study staff, it will be discussed with the study staff and 
will be addressed on a case-by-case basis. The PI will be notified of any complaints. Complaints 
will be reported to the IRB if indicated. 
If the subject has questions about his or her rights as a study subject, wants to report any 
problems or complaints, obtain information about the study, or offer input, the subject can call the 
Medical College of Wisconsin/Froedtert Hospital research subject advocate at 414-955-8844. 
This information is provided to the subject in their consent. 
6.5 Product Complaint 


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A product complaint is a verbal, written, or electronic expression that implies dissatisfaction 
regarding the identity, strength, purity, quality, or stability of a drug product. Individuals who 
identify a potential product complaint situation should immediately contact the Drug Manufacturer 
and report the event. Whenever possible, the associated product should be maintained in 
accordance with the label instructions pending further guidance from a Drug Manufacturer 
representative. Product complaints in and of themselves are not Reportable Events. If a product 
complaint results in an SAE, an SAE form should be completed. All product complaints must be 
reported to CTI within 24 hours of study staff awareness at productcomplaints@ctibiopharma.com 
7 PHARMACEUTICAL INFORMATION
7.1 Product Description 
Pacritinib for oral administration is supplied in capsules containing 100 mg (as the free base) in 
red cap/gray body size 0 opaque hard gelatin capsules. The inactive ingredients are 
microcrystalline cellulose, magnesium stearate, and polyethylene glycol 8000. Each capsule 
contains 146 mg of pacritinib citrate, which is equivalent to 100-mg pacritinib free base.
Pacritinib capsules should not be opened or crushed. Direct contact of the powder in pacritinib 
capsules with the skin or mucous membranes should be avoided. If such contact occurs, affected 
areas should be washed thoroughly with water.
7.2 Mechanism of Action
Pacritinib is a macrocyclic Janus kinase inhibitor that is being developed for the treatment of 
myelofibrosis. It mainly inhibits Janus kinase 2 (JAK2) and Fms-like tyrosine kinase 3 (FLT3). 
7.3 Product Supply
Pacritinib will be supplied in 100-mg capsules by CTI BioPharma. 
7.4 Storage Conditions
The drug product should be stored in the pharmacy, hospital, clinic, or warehouse at controlled 
room temperature, 20°C to 25°C (68°F to 77°F), with excursions between 15°C and 30°C (59°F 
and 86°F) allowed. Patients should be instructed that storage temperatures for pacritinib in the 
home should be below 30°C (86°F). 
7.5 Handling and Drug Accountability
The investigator is fully responsible for the investigational products at the trial site. Dispensing of 
investigational products will be delegated to delegated site staff. The person responsible for 
dispensing the investigational products will be responsible for maintaining adequate control of the 
investigational products and for documenting all transactions with them.
The investigator, or a responsible party designated by the investigator, will maintain a careful 
record of the inventory and disposition of all agents. Each participating site investigator, or 
authorized designee, is responsible for maintaining a careful record of inventory and disposition 
of all investigational agents received at the site. Use of the NCI Drug Accountability Record Form 
is recommended, but sites may use their own accountability logs per institutional standards. Sites


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must ensure accountability records capture the same information as the NCI Drug Accountability 
Record Form and in addition, capture the preparation time. Any used or partially used vials may 
be destroyed on-site per the institutional standard of practice. Expired vials remaining at the end 
of the study may be destroyed onsite per institutional standards.
At every study visit, patients will return bottles in which pacritinib is supplied with all remaining 
untaken pacritinib capsules, if any. Patient compliance will be evaluated by pill count and through 
pill diary provided at each visit. (Appendix 10)
Patients on the study will maintain a “Subject Diary” to record the number of tablets/pills/capsules 
of study medications they take daily. On this diary, they will also record any side effects related 
to the study medications.
7.6 Contraindications
Supportive care therapies, except when prohibited by any of the below provisions, are permitted, 
including the use of low-dose aspirin. Corticosteroids (up to 20 mg/day of prednisone or 
equivalent) and/or hydroxyurea may be used for up to two weeks during the first month of 
treatment with pacritinib. 
The following therapies and procedures are prohibited throughout the study: 
Antiplatelet or anticoagulati
.
Growth factor therapies, including erythropoietin and thrombopoietin.
Strong CYP3A4 inhibitors and strong CYP450 inducers, except as needed to treat AEs, 
with study PI approval.
Any drugs with significant potential for QTc prolongation (Appendix 6), except as needed 
to treat AEs, with medical monitor approval.
Splenic irradiation or splenectomy.
Ongoing Hemorrhage: Patients with active bleeding should not begin or continue treatment with 
pacritinib. Reports of serious bleeding events, including life-threatening and fatal events, have 
been reported in association with pacritinib use. Pacritinib should be discontinued before planned 
surgery.
Hypersensitivity: Patients with a known hypersensitivity to the active ingredient or any of the 
excipients of the drug product should not take pacritinib.
7.7 Known Adverse Events
Based on the adverse effects observed in nonclinical toxicity studies, as well as data from clinical 
studies in patients with advanced MF, AML, and lymphoma, the investigator is advised to observe 
the following precautions:
Gastrointestinal: Diarrhea has been reported during treatment with pacritinib and generally 
occurs within the first eight weeks of treatment. Pacritinib-related diarrhea is usually low grade, 
with severe diarrhea (grade 3 or 4) occurring in 5.8% of patients. Early identification and 
intervention are critical for the optimal management of diarrhea. Antidiarrheal medications should 
be given to patients starting on pacritinib, with instructions to start taking to control symptoms at 
the first sign of diarrhea. Pre-existing diarrhea should be adequately controlled before beginning


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therapy. Nausea, vomiting, and abdominal pain have also been reported in relation to pacritinib 
administration. Most cases were reported to be of low severity, and symptoms improved with 
supportive management without requiring discontinuation of treatment. Patients with significant 
GI symptoms despite optimal supportive care may have pacritinib interrupted or have the dose of 
pacritinib reduced per protocol.
Platelet Count Reduction: Clinically relevant decreases in platelet count have been observed in 
patients treated with pacritinib. Prior to initiating treatment, patients should undergo laboratory 
testing to establish their baseline hematology profile, including complete blood count with a white 
blood cell count differential, platelet count, and coagulation testing, including prothrombin, 
international normalized ratio, partial thromboplastin time, and thrombin time. While on pacritinib, 
patients should be monitored as specified in the protocol for severe thrombocytopenia. For 
clinically significant decreases in platelet count, the dose of pacritinib should be reduced or
interrupted in accordance with protocol guidelines.
Bleeding: Pacritinib may increase the risk of bleeding. Reports of serious bleeding events, 
including life-threatening and fatal events, have been reported. These bleeding events were 
generally without lasting sequelae, although life-threatening and fatal events of hemorrhage, 
including intracranial hemorrhage, were observed more frequently in pacritinib-treated patients 
compared with BAT patients. Risk factors for bleeding with pacritinib may include prior bleeding 
events and anti-platelet and anti-coagulant medications in addition to severe thrombocytopenia.
Concomitant use of drugs affecting hemostasis, such as aspirin and other antiplatelet agents, 
other anticoagulants, heparin, and thrombolytic agents, may increase the risk of bleeding. Refer 
to the protocol for guidance on dose modifications for pacritinib-related bleeding events.
Cardiac: QTc prolongation has been observed in patients treated with pacritinib. Prior to initiating 
treatment with pacritinib, patients should undergo an ECG to establish baseline QTc and an 
echocardiogram (or other appropriate methodology) to establish baseline left ventricular ejection 
fraction; patients should be monitored periodically for changes in their QTc. Pacritinib should not 
be used in patients with uncontrolled cardiac dysrhythmias, QTc prolongation >450 ms, or other 
factors that
increase the risk for QT prolongation (e.g., heart failure, hypokalemia,
hypomagnesemia, or a history of long QT interval syndrome). Caution should be used when co-
administering other medicinal products with the potential to elongate QT interval. Ejection fraction 
should be monitored at baseline, after one month on treatment, after three and six months on 
treatment, and every six months thereafter; pacritinib dose should be modified if significantly 
reduced ejection fraction is detected. Additional ECG and ejection fraction assessments should 
be performed as clinically indicated. Refer to the protocol for guidance on dose modifications for
pacritinib-related QTc prolongation.
General: Additional AEs commonly (>10% of patients) reported during pacritinib administration 
include fatigue, peripheral edema, pyrexia, decreased appetite, and pruritus. Adverse events and 
SAEs in the SOC of infections and infestations have been frequently reported, but none of these 
events were considered atypical for this population. Neoplasms, typically nonmelanoma skin 
cancers, have been reported in patients treated with pacritinib and were clustered in patients with 
geographic and other risk factors for skin malignancy, making further conclusions difficult.
Participants in clinical studies of pacritinib will be monitored closely for these AEs.


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8 STATISTICAL CONSIDERATIONS
8.1 Study Populations
Efficacy population — all enrolled subjects who received at least one dose of the study drug and 
have either died or have at least one evaluation of PSA after the initiation of study treatment.
Safety population — all enrolled subjects who received at least one dose of the study drug. 
8.2 Study hypotheses
The null hypothesis that the median PSA-progression-free survival is six months will be tested 
against a one-sided alternative by for the six-month PSA-progression-free survival probability 
exceeding 50%. The study is designed to have 80% power to obtain a result significant at a one-
sided 10% level if the experimental treatment has a six-month PSA-progression-free probability 
of 66%, which corresponds to a median of 10 months if the time to PSA progression is 
exponentially distributed.(84)
8.3 Study design and sample size
A two-stage single-arm design based on the methods of Huang et al (2010) will be used.
The design is based on a modification of a binomial two-stage design that allows the incorporation 
of data from subjects with less than six months of follow-up at the interim analysis. The study will 
enroll up to 46 subjects with an interim analysis performed when 10 patients have been treated 
and followed for 6 months. The underlying binomial design would stop for futility if there are four
or fewer patients alive without PSA progression at six months among these 10 patients. The 
modified futility decision will use the Kaplan-Meier estimate of the six-month PSA-progression-
free survival using the data from the first 10 subjects and any subject who have been enrolled 
during the six-month follow-up period of the tenth subject. If the six-month PSA-progression-free 
survival is significantly lower at a one-sided 10% significance level than the clinically meaningful 
value of 66% defined by the alternative hypothesis, the study will be stopped for futility. If no new 
patients would be enrolled during the follow-up period, this decision rule is equivalent to the one 
defined by the binomial design.
If the study is not stopped for futility, study enrollment continues until 46 subjects are enrolled. 
The final analysis will be performed when all subjects have been followed for at least six months. 
The null hypothesis will be rejected, and the study drug will be considered promising if 27 or more 
patients are alive without PSA progression at six months among the 46 patients. The underlying 
binomial design yields a type I error rate of 10% if the underlying six-month PSA-progression-free 
probability is 50% (and the median PSA-progression-free survival is 6 months), and power of 80% 
when the six-month PSA-progression-free probability is 66%, which corresponds to a median of 
10 months if the time to PSA progression is exponentially distributed. Simulation studies 
confirmed that the design with the modified futility stopping method maintains these properties. If 
the median PSA-progression-free survival is six months, then the binomial design would stop at 
the interim analysis with 38% probability. Assuming an enrollment rate of 1.5 subjects/month, the 
modified futility stopping rule increases this probability of stopping at the interim analysis to 45%.


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8.4 Analysis of primary endpoint
The probability of PSA-progression-free survival over time will be estimated using the Kaplan-
Meier method and shown with 80% pointwise confidence limits. The six-month PSA-progression-
free survival will be compared to the null-value of 50% using a z-test at a one-sided 10% 
significance level. 
8.5 Analysis of secondary endpoints
The PSA nadir values will be summarized with mean and standard deviation as absolute values 
and as percent change from baseline PSA value. The time to PSA nadir and time to subsequent 
antineoplastic therapy will be summarized using Kaplan-Meier (KM) curves. The median will be 
estimated using the inverse-KM method and shown with 95% confidence intervals. The change 
in testosterone levels from baseline to cycle 4 will be shown graphically using box-plots and 
reported with mean and standard deviation.
8.6 Analysis of exploratory endpoints
The analysis of Comprehensive Geriatric Assessment domains will be descriptive and will 
describe mean, median, standard deviations of scores at baseline and at follow up time points.  
CGA deficits over 6 months will be captured. Each domain will be evaluated individually, and 
scores will be compared between baseline and 6 months. Overall CGA deficits will be examined 
and the proportion of patients who decline in more than 1 domain will be determined for these 
time points.
For each of the 27 core items and 12 site-specific items of the FACT-P tool, mean score for the 
study cohort will be computed at baseline and at specified follow-up visits (Section 8). These 
means will be plotted against follow-up time and visually assessed for evidence of an upward or 
a downward trend. For each item, an upward or a downward trend in mean scores over time will 
indicate improvement or deterioration in a given dimension of quality of life (i.e., the dimension 
measured by that item). Changes in mean scores from baseline will be calculated at three months 
and six months after therapy initiation and will be reported with 95% confidence intervals.
8.7 Safety analyses
Safety and toxicities of the study drug will be examined by documenting the type and grade of 
each adverse event (as defined by CTCAE v5, at baseline, and each follow-up visit). These data 
will be summarized with counts and percentages. In addition, each grade 3 or 4 adverse event
will be described separately, and the plausibility of its causation by the study drug combination 
will be discussed.
8.8 Other analyses
Demographic and clinical characteristics of the patient population will be reported using 
appropriate descriptive statistics such as frequencies and percentages with standard errors for 
categorical variables, mean with standard error or median with quartiles for continuous variables.
The disposition of each subject will be reported as a listing.


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8.9 Interim analyses
An interim analysis for futility will be performed when 10 patients have been treated and followed 
for six months. The Kaplan-Meier estimate of the six-month PSA-progression-free survival using 
the data from the first 10 subjects and any subject who have been enrolled during the six-month 
follow-up period of the tenth subject will be computed and compared to 66% using a z-test at a 
one-sided 10% significance level. The study will be stopped for futility if the hypothesis is rejected 
for the alternative of the 6-month PSA-progression-free survival being lower than 66%.
8.10 Missing data
For all outcomes, summary statistics will include the count of missing and non-missing values. 
Patients with missing value for the primary outcome, PFS, will be censored at the time when last 
known to be alive and without progression. A similar approach will be used for other time-to-event 
outcomes, such as time to PSA nadir. Secondary outcomes requiring numeric values, such as 
geriatric assessments, PSA and testosterone levels will be analyzed among patients with non-
missing values as required for each analysis (e.g., non-missing value at specific time point for 
cross-sectional analysis, and non-missing values at two time points for change analyses). The 
limitations of extensive missingness, if present, will be clearly noted in all reports and any related 
findings will be interpreted with caution.
9 DATA AND SAFETY MONITORING PLAN (DSMP)
9.1 Data and Safety Management Overview
The Medical College of Wisconsin (MCW) Data Safety Monitoring Committee (DSMC) and the 
MCW Institutional Review Board (IRB) will approve protocol-specific DSM plans. A local, 
investigator-initiated trial will be required to be continuously monitored by the principal investigator 
of the study with safety and progress reports submitted to the DSMC. 
The DSMP for this study will involve the following entities:
9.2 Study Team
The study team minimally consists of the principal investigator, the clinical research coordinator, 
regulatory specialist, and the study biostatistician. While subjects are on study, the principal 
investigator will meet regularly with the research coordinator and the study biostatistician to review 
study status. This review will include but not be limited to reportable SAEs and UPIRSOs and an 
update of the ongoing study summary that describes study progress in terms of the study schema. 
The appropriateness of further subject enrollment and the specific intervention for the next subject 
enrollment is addressed. All meetings including attendance are documented. 
9.3 Quality Assurance 
The MCWCC Clinical Trials Office provides ongoing quality assurance audits. This protocol was 
classified as intermediate risk and will be reviewed internally by the MCW Cancer Center 
Clinical Trials Office Quality Assurance Staff according to the MCWCC Data and Safety 
Monitoring Plan and current version SOP, 6.5.2 Internal Quality Assurance Reviews. 
.


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9.4 Clinical Trials Office
The MCWCC Clinical Trials Office [CTO] provides administrative assistance and support to the 
DSMC. 
9.5 DSMC
The Medical College of Wisconsin Cancer Center places the highest priority on ensuring the 
safety of patients participating in clinical trials. Every cancer interventional trial conducted at MCW 
includes a plan for safety and data monitoring.
More information can be found related to the MCWCC Data and Safety Monitoring Plan at the 
MCWCC website (Data and Safety Monitoring Plan). 
This study will be reviewed by the Medical College of Wisconsin Cancer Center Data and Safety 
Monitoring Committee (MCWCC DSMC). A summary of the MCWCC DSMC activities are as 
follows: 
Review the clinical trial for data integrity and safety 
Review all DSM reports
Submit a summary of any recommendations related to study conduct 
Terminate the study if deemed unsafe for patients 
A copy of the MCWCC Data and Safety Monitoring Plan and membership roster will be maintained 
in the study research file and updated as membership changes. The committee will review reports 
from the study PI twice annually (or more frequently if needed) and provide recommendations on 
trial continuation, suspension, or termination as necessary. 
Any available DSMC letters will be submitted to the IRB of record as required.
10 REGULATORY COMPLIANCE, ETHICS, AND STUDY
MANAGEMENT
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki as stated in 21 CFR §312.120(c)(4); consistent with GCP and all 
applicable regulatory requirements.
10.1 Regulatory Compliance
This study will be conducted in compliance with:
The protocol
Federal regulations, as applicable, including 21 CFR 50 (Protection of Human 
Subjects/Informed Consent); 21 CFR 56 (Institutional Review Boards) and 45 CFR 46 
Subparts A (Common Rule), B (Pregnant Women, Human Fetuses and Neonates), C 
(Prisoners), and D (Children), GCP/ICH guidelines, and all applicable regulatory 


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requirements. The IRB must comply with the regulations in 21 CFR §56 and applicable 
regulatory requirements.
10.2 Prestudy Documentation 
Prior to implementing this protocol at MCWCC, the protocol, informed consent form, HIPAA 
authorization and any other information pertaining to participants must be approved by the MCW 
IRB. 
The clinical investigation will not begin until the Investigator has received a letter from the FDA 
stating that the study is exempt from IND requirements. 
10.3 Institutional Review Board
The protocol, the proposed informed consent form, and all forms of participant information related 
to the study (e.g., advertisements used to recruit participants) will be reviewed and approved by 
the MCW Institutional Review Board. Before obtaining MCW approval, the protocol must be 
approved by the Medical College of Wisconsin Cancer Center Scientific Review Committee. The 
initial protocol and all protocol amendments must be approved by the IRB before implementation. 
Informed Consent Process
Informed consent is a process that is initiated prior to the individuals agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks 
and possible benefits of this therapy will be provided to the subjects and their families. Consent 
forms describing in detail the study interventions/products, study procedures, and risks are given 
to the subject and written documentation of informed consent is required prior to starting 
intervention/administering study product.
Consent forms will be IRB-approved and the subject (and Legally Authorized Representative, if 
necessary) will be asked to read and review the document. Upon reviewing the document, the 
investigator will explain the research study to the subject and answer any questions that may 
arise. In accordance with 46 CR 46.111, the subject will sign and date the informed consent 
document prior to any procedures being done specifically for the study. 
A witness should only sign when required, per FH/MCW IRB policy. If a witness signs the 
document when not required, the study staff should document in the legal medical record (or note 
to file) the relationship to the patient and why a witness signed. (i.e., “Although not required, the 
subject’s spouse was present during the consenting process and signed as the witness.” Or 
“Although not required, the hospital staff was present for the consenting process and signed as a 
witness.”)
The subjects will have the opportunity to discuss the study with their surrogates or think about it 
prior to agreeing to participate. The subjects may withdraw consent at any time throughout the 
course of the trial. 
A copy of the informed consent document will be given to the subjects for their records. The rights 
and welfare of the subjects will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. If there are 
changes to the consent form, all revisions will be reviewed with the study subject at the next 
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amendment submission. The process for obtaining informed consent will again be performed. 
Study subjects will not be reconsented for continuing reviews. The MCWCC CTO will follow the 
MCW/FH IRB’s policy for subjects who demonstrate limited English proficiency or limited literacy. 
After the subject’s visit in which the consent is signed, it is documented in the clinic chart that the 
consent has been signed and that all questions have been answered to the subject’s satisfaction 
after adequate time for the review of the consent. It is also documented that a copy of the consent 
is given to the subject. The original consent is kept with the subject’s study file, and a copy of the 
consent is sent to the OCRICC office, which will then submit to HIM a copy of the signed consent 
to be scanned into EPIC, the legal medical record.
10.4 Subject Confidentiality and Access to Source Documents/Data
Subject confidentiality is strictly held in trust by the sponsor-investigator, participating 
investigators, and any staff, [and the sponsor(s) and their agents] (include bracketed portion if 
applicable). This confidentiality includes clinical information relating to participating subjects, as 
well as any genetic or biological testing.
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the principal investigator.
The conditions for maintaining the confidentiality of the subjects’ records are required for the life 
of the data. These rules apply equally to any and all MCWCC projects. 
One risk of taking part in a research study is that more people will handle the personal health 
information collected for this study. The study team will make every effort to protect the information 
and keep it confidential, but it is possible that an unauthorized person might see it. Depending on 
the kind of information being collected, it might be used in a way that could embarrass the subject 
or affect his/her ability to get insurance.
While data are being collected and after all data have been collected but are still in the process 
of being analyzed, the subject’s data/PHI are stored in the locked Clinical Research office in the 
Clinical Trials Office. Databases in which the study subject information is stored and accessed 
are password-protected, allowing for limited access by authorized personnel only. Data/PHI kept 
in the Case Report Forms contain the study identifiers, subject initials, date of birth and date of 
service. 
The principal investigator will allow access to all source data and documents for the purposes of 
monitoring, audits, IRB review, and regulatory inspections. 
The study monitor/s or other authorized representatives of the principal investigator may inspect 
all documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. 
The clinical study site will permit access to such records.
10.5 Protection of Human Subjects
10.5.1 Protection from Unnecessary Harm


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Each clinical site is responsible for protecting all subjects involved in human experimentation. This 
is accomplished through the IRB mechanism and the informed consent process. The IRB reviews 
all proposed studies involving human experimentation and ensures that the subject’s rights and 
welfare are protected and that the potential benefits and/or the importance of the knowledge to 
be gained outweigh the risks to the individual. The IRB also reviews the informed consent 
document associated with each study to ensure that the consent document accurately and 
communicates the nature of the research to be done and its associated risks and benefits.
10.5.2 Protection of Privacy
As noted, patients will be informed of the extent to which their confidential health information 
generated from this study may be used for research purposes. Following this discussion, they will 
be asked to sign informed consent documents. The original signed document will become part of 
the patient’s medical records, and each patient will receive a copy of the signed document. 
10.5.3 Changes in the Protocol
Once the protocol has been approved by the MCW IRB, any changes to the protocol must be 
documented in the form of an amendment. The amendment must be signed by the investigator 
and approved by IRB prior to implementation. 
If it becomes necessary to alter the protocol to eliminate an immediate hazard to patients, an 
amendment may be implemented prior to IRB approval. In this circumstance, however, the 
Investigator must then notify the IRB in writing within five working days after implementation.
The IRB may provide, if applicable regulatory authority(ies) permit, expedited review, and 
approval/favorable opinion for minor change(s) in ongoing studies that have the approval 
/favorable opinion of the IRB. The investigator will submit all protocol modifications to the sponsor 
and the regulatory authority(ies) in accordance with the governing regulations.
Changes to the protocol may require approval from the sponsor.
Any departures from the protocol must be fully documented in the source documents.
10.6 Investigator Compliance 
The investigator will conduct the study in compliance with the protocol given approval/favorable 
opinion by the IRB and the appropriate regulatory authority(ies). 
Onsite Audits
Auditing is essential to ensure that research conducted at the Medical College of Wisconsin 
(MCW) Cancer Center is of the highest quality and meets MCW and regulatory agency standards. 
Regulatory authorities, the IRB and/or sponsor may request access to all source documents, data 
capture records and other study documentation for on-site audit or inspection. Direct access to 
these documents must be guaranteed by the investigator, who must provide support at all times 
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11 DATA HANDLING AND RECORD KEEPING
11.1 Overview
Every effort is made to uphold the integrity of the project, the research, the institution, and the 
researchers involved. Data collection guidelines and methodologies are carefully developed 
before the research begins. Investigators focus on the following to ensure data integrity:  well-
trained data collectors/recorders to ensure consistency and quality, well-designed data collection 
protocols and ongoing monitoring. In this way, study rigor and validity are maintained. Data is 
protected from physical damage as well as from tampering, loss, or theft. This project’s data 
management is a multidisciplinary activity that includes investigators, research coordinators and 
nurses, data mangers, support personnel, biostatisticians, and database programmers. Quality 
control will be applied to each stage of data handling to ensure that all data are reliable and have 
been processed correctly. 
11.2 Data Management Responsibilities
Principal Investigator
The principal investigator oversees the management of patient records/case report forms and 
ensures that a) complete and accurate data will be obtained and provided to the sponsor; b) 
patient records are maintained to include history, prescribed medication, and investigational 
product(s), measurements, exams, evaluations, and adverse events; c) corrections are applied 
to clinical research data according to principles of good research practice (i.e., single-line delete, 
date and initial). He or she will ensure that there is a correlation between the case report forms 
and the source documents.
Research Coordinator
A research coordinator creates, collects, and organizes clinical trial documentation. He or she 
ensures that source documentation and data abstraction and entry are being done at protocol-
specified time points.
Research Nurse/Medical Staff
The research nurse and medical staff documents protocol-required care or assessment of the 
subject’s outcomes, adverse events, and compliance to study procedures.
Biostatistician
The biostatistician may assist in CRF development (content and design), dataset specifications 
(annotation of CRFs and record layout) and validation.
11.3 Source Documents
Source documents for clinical information (patient history, diagnosis, clinical and diagnostic test 
reports, etc.) are maintained in the patient’s clinical file. 
All source documents will be written following ALCOA standards: 
ALCOA Attribute
Definition
Attributable
Clear who has documented the data.
Legible
Readable and signatures identifiable.


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Contemporaneous
Documented in the correct time frame along with the flow of events. 
If a clinical observation cannot be entered when made, chronology 
should be recorded. Acceptable amount of delay should be defined 
and justified.
Original 
Original, if not original should be exact copy; the first record made 
by the appropriate person. The investigator should have the 
original source document.
Accurate
Accurate, consistent and real representation of facts.
Enduring
Long-lasting and durable.
Available and 
accessible
Easily available for review by treating physicians and during 
audits/inspections. The documents should be retrievable in 
reasonable time.
Complete
Complete until that point in time.
Consistent
Demonstrate the required attributes consistently.
Credible
Based on real and reliable facts.
Corroborated
Data should be backed up by evidence.
11.4 Case Report Forms 
The principal investigator and/or his/her designee will prepare and maintain adequate and 
accurate participant case histories with observations and data pertinent to the study. Study-
specific Case Report Forms (CRFs) will document outcomes. All study data will be entered into 
OnCore® via standardized CRFs, in accordance with the study calendar, using single data entry 
with a secure access account. The Clinical Research Coordinator will complete the CRFs as soon 
as possible upon completion of the study visit; the investigator will review and approve the 
completed CRFs. 
The information collected on CRFs shall be identical to that appearing in original source 
documents. Source documents will be found in the patient’s medical records maintained by 
MCWCC personnel. All source documentation should be kept in separate research folders for 
each patient.
In accordance with federal regulations, the investigator is responsible for the accuracy and 
authenticity of all clinical and laboratory data entered onto CRFs. The principal investigator will 
approve all completed CRFs to attest that the information contained on the CRFs is true and 
accurate. 
All source documentation and data will be available for review/monitoring by the MCWCC DSMC 
and regulatory agencies.
11.5 Study Record Retention
The principal investigator is required to maintain adequate records.
The principal investigator is required to prepare and maintain adequate and accurate case 
histories that record all observations and other data pertinent to the investigation.
Case histories include the case report forms and supporting data including, for example, signed 
and dated consent forms and medical records including, for example, progress notes of the 
physician, the individual's hospital chart(s), and the nurses' notes. The case history for each 
individual shall document that informed consent was obtained prior to participation in the study.


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Study documentation includes all CRFs, data correction forms or queries, source documents, 
sponsor-investigator correspondence, monitoring logs/letters, and regulatory documents (e.g., 
protocol and amendments, IRB correspondence and approval, signed patient consent forms).
Source documents include all recordings of observations or notations of clinical activities and all
reports and records necessary for the evaluation and reconstruction of the clinical research study.
 


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APPENDIX 1. PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
0
Normal activity
Fully active, able to carry on all 
pre-disease performance 
without restriction
100
Normal, no complaints, no evidence 
of disease
90
Able to carry on normal activity; 
minor signs or symptoms of the 
disease
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)
80
Normal activity with effort; some 
signs or symptoms of the disease
70
Cares for self, unable to carry on 
normal activity or to do active work
2
In bed < 50% of the time
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities
Up and about more than 50% of 
waking hours
60
Requires occasional assistance, but 
is able to care for most of his/her 
needs
50
Requires considerable assistance 
and frequent medical care
3
In bed > 50% of the time
Capable of only limited self-
care, confined to bed or chair 
more than 50% of waking hours
40
Disabled, requires special care and 
assistance
30
Severely disabled, hospitalization 
indicated
Death not imminent
4
100% bedridden
Completely disabled
Cannot carry on any self-care
Totally confined to bed or chair
20
Very sick, hospitalization indicated
Death not imminent
10
Moribund, fatal processes 
progressing rapidly
5
Dead
0
Dead


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APPENDIX 2. LOST TO FOLLOW-UP LETTER
Date: ___________________________________
Dear ___________________________________,
The research study team has been unable to contact you regarding the clinical trial (A Phase 2 
Study of Pacritinib for the Management of Patients with Biochemical Relapse after Definitive 
Treatment for Prostate Cancer) you participated in.
We would like to discuss how you are doing and if we may continue contacting you.
Please contact us at _____________________________________________________________
Sincerely,
___________________________________


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APPENDIX 3. SELECTED STRONG INHIBITORS OF CYP3A4
Boceprevir                         ciprofloxacin               clarithromycin
Conivaptan                        erythromycin                fluconazole
Grapefruit                          grapefruit juice             indinavir
Itraconazole                       ketoconazole               lopinavir
Mibefradil                           nefazodone                 nelfinavir
Norfloxacin                         posaconazole             Quinidine      
Ritonavir                             saquinavir                   Seville oranges
star fruit                               telaprevir                     telithromycin
troleandomycin                   voriconazole
This list is not comprehensive. When considering using an agent that could be a potential CYP3A4 
inhibitor, please discuss this with the pharmacy team.
Source: http://medicine.iupui.edu/clinpharm/ddis/table.asp and 
http://www.pharmacytimescom/issue/pharmacy/2008/2008-
09/2008-09-8687.


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APPENDIX 4. SELECTED STRONG INDUCERS OF CYP450
carbamazepine
efavirenz
nevirapine
phenobarbital
phenytoin
pioglitazone
rifabutin
rifampin
St. John's Wort
Troglitazone
This list is not comprehensive. When considering using an agent that could be a potential CYP450 
inducer, please discuss this with the pharmacy team.
.
Source: http://medicine.iupui.edu/clinpharm/ddis/table.asp and 
http://www.pharmacytimescom/issue/pharmacy/2008/2008-
09/2008-09-8687.


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APPENDIX 5. THE STAGES OF HEART FAILURE, NEW YORK HEART 
ASSOCIATION CLASSIFICATION
To determine the best course of therapy, physicians often assess the stage of heart failure according 
to the New York Heart Association (NYHA) functional classification system. This system relates 
symptoms to everyday activities and the patient’s quality of life.
Class
Patient Symptoms
I (Mild)
No limitation of physical activity. Ordinary 
physical activity does not cause undue 
fatigue,
palpitation, or dyspnea (shortness of breath).
II (Mild)
Slight limitation of physical activity. 
Comfortable at rest, but ordinary physical 
activity results in fatigue, palpitation, or 
dyspnea.
III (Moderate)
Marked limitation of physical activity. 
Comfortable at rest, but less-than-ordinary 
activity causes fatigue, palpitation, or 
dyspnea.
IV (Severe)
Unable to carry out any physical activity 
without discomfort. Symptoms of cardiac
insufficiency at rest. If any physical activity is 
undertaken, discomfort is increased
Source: Dolgin M, Fox AC, Devereaux RB. Nomenclature and criteria for diagnosis of diseases of 
the heart and great vessels. 9th ed. Boston: Little Brown and Company; 1994. p. 253-256


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APPENDIX 6. MEDICATIONS WITH SIGNIFICANT ARRHYTHMOGENIC 
POTENTIAL
Use of the following drugs is prohibited due to the potential for QT interval prolongation.a
Alkylating agent
Bendamustine (Treanda, Treakisym, Ribomustin, Levact)
Alpha 1 blocker
Alfuzosin (Uroxatral)
Analgesic
Hydrocodone-ER (Hysingla™ ER, Zohydro ER); Tramadol (Crispin, 
Ralivia ER, Ralivia Flashtab, Tramadolum, Tramal, Tramodol, Tridural, 
Ultram, Ultram ER, Zydol)
Anesthetic
Propofol (Diprivan, Propoven); Sevoflurane (Ultane, Sojourn)
Antianginal
Bepridil (Removed from Market) (Vascor)
Antiarrhythmic
Amiodarone 
(Cordarone, 
Pacerone, 
Nexterone); 
Disopyramide 
(Norpace); Dofetilide (Tikosyn); Dronedarone (Multaq); Flecainide 
(Tambocor, Almarytm, Apocard, Ecrinal, Flécaine); Ibutilide (Corvert); 
Procainamide (Pronestyl, Procan); Quinidine (Quinaglute, Duraquin, 
Quinact, Quinidex, Cin-Quin, Quinora); Sotalol (Betapace, Sotalex, 
Sotacor); Pilsicainide (Only on Non-US Market) (Sunrythm)
Antibiotic
Azithromycin (Zithromax, Zmax); Bedaquiline (Sirturo); Ciprofloxacin 
(Cipro, 
Cipro-XR, Neofloxin); 
Clarithromycin (Biaxin, Prevpac); 
Delamanid (Only on Non US Market) (Deltyba); Erythromycin (E.E.S., 
Robimycin, EMycin, Erymax, Ery-Tab, Eryc Ranbaxy, Erypar, Eryped, 
Erythrocin Stearate Filmtab, Erythrocot, E-Base, Erythroped, Ilosone, 
MY-E, Pediamycin, Abboticin, Abboticin-ES, Erycin, PCE Dispertab, 
Stiemycine, Acnasol, Tiloryth); Gatifloxacin (Removed from Market) 
(Tequin); Gemifloxacin (Factive); Grepafloxacin (Removed from Market) 
(Raxar); Levofloxacin (Levaquin, Tavanic); Moxifloxacin (Avelox, 
Avalox, Avelon); Norfloxacin (Removed from Market) (Noroxin, 
Ambigram); Ofloxacin (Floxin); Roxithromycin (Only on Non US Market) 
(Rulide, Xthrocin, Roxl-150, Roxo, Surlid, Rulide, Biaxsig, Roxar, 
Roximycinv, Roxomycin,
Rulid, Tirabicin, Coroxin); Sparfloxacin 
(Removed from Market) (Zagam); Telavancin (Vibativ); Telithromycin 
(Ketek);
Anticancer
Arsenic trioxide (Trisenox); Capecitabine (Xeloda); Lenvatinib 
(Lenvima); Tamoxifen (Nolvadex [discontinued 6/13], Istubal, 
Valodex); Vandetanib (Caprelsa); Cabozantinib (Cometriq); Epirubicin 
(Ellence, Pharmorubicin, Epirubicin Ebewe); Fluorouracil (5-FU) 
(Adrucil, Carac, Efudex, Efudix, others); Midostaurin (Rydapt); 
Necitumumab (Portrazza); Tipiracil and Trifluridine (Lonsurf)
Anticoagulant
Betrixaban (Bevyxxa)
Anticonvulsant
Ezogabine (Retigabine) (Potiga, Trobalt); Felbamate (Felbatol)


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Antidepressant
SNRI: Venlafaxine (Effexor, Efexor)
SSRI: Citalopram (Celexa, Cipramil); Escitalopram (Cipralex, Lexapro, 
Nexito, Anxiset-E [India], Exodus [Brazil], Esto [Israel], Seroplex, Elicea, 
Lexamil, Lexam, Entact [Greece], Losita [Bangladesh], Reposil [Chile], 
Animaxen [Colombia], Esitalo [Australia], Lexamil [South Africa])
Tetracyclic: Mirtazapine (Remeron)
Tricyclic: 
Clomipramine 
(Anafranil); 
Desipramine 
(Pertofrane, 
Norpramine); Imipramine (melipramine) (Tofranil); Nortriptyline 
(Pamelor, Sensoval, Aventyl, Norpress, Allegron, Noritren, Nortrilen); 
Trimipramine (Surmontil, Rhotrimine, Stangyl)
Antiemetic
Dolasetron 
(Anzemet); 
Granisetron 
(Kytril, 
Sancuso, 
Granisol); 
Ondansetron (Zofran, Anset, Ondemet, Zuplenz, Emetron, Ondavell, 
Emeset, Ondisolv, Setronax); Palonosetron (Aloxi); Tropisetron (Only on 
Non US Market) (Navoban, Setrovel)
Antifungal
Fluconazole (Diflucan, Trican); Pentamidine (Pentam)
Antihistamine
Astemizole (Removed from Market) (Hismanal); Terfenadine (Removed 
from Market) (Seldane)
Antihypertensive
Isradipine (Dynacirc); Ketanserin (Only on Non US Market) (Sufrexal); 
Moexipril/HCTZ (Uniretic, Univasc); Nicardipine (Cardene)
Antilipemic
Probucol (Removed from Market) (Lorelco)
Antimalarial
Artenimol+piperaquine 
(Only 
on 
Non-US 
Market) 
(Eurartesim); 
Chloroquine (Aralen); Halofantrine (Only on Non-US Market) (Halfan); 
Primaquine phosphate
Antimania
Lithium (Eskalith, Lithobid)
Antimycobacterial
Clofazimine (Only on Non-US Market) (Lamprene)
Antinausea
Domperidone (Only on Non-US Market) (Motilium, Motillium, Motinorm 
Costi, Nomit)
Antineoplastic agent
Inotuzumab ozogamicin (Besponsa); Oxaliplatin (Eloxatin)
Antipsychotic
Cyamemazine (cyamepromazine) (Only on Non-US Market) (Tercian); 
Haloperidol (Haldol [US & UK], Aloperidin, Bioperidolo, Brotopon, Dozic, 
Duraperidol [Germany], Einalon S, Eukystol, Halosten, Keselan, Linton, 
Peluces, 
Serenace, 
Serenase, 
Sigaperidol); 
Levomepromazine 
(methotrimeprazine) (Only on Non-US Market) (Nosinan, Nozinan, 
Levoprome); Levosulpiride (Only on Non-US Market) (Lesuride, Levazeo, 
Enliva [with rabeprazole]; Mesoridazine (Removed from Market) (Serentil); 
Perphenazine (Trilafon, Etrafon/Triavil, Decentan); Pimozide (Orap); 
Pipamperone (Only on Non-US Market) (Dipiperon [E.U], Propitan [Japan], 
Dipiperal, Piperonil, Piperonyl); Prothipendyl (Only on Non-US Market) 
(Dominal, Largophren, Timoval, Timovan, Tumovan); Thioridazine 
(Mellaril, Novoridazine, Thioril); Benperidol (Only on Non-US Market) 


Study Short Title: IIT-Kilari-J31001-BLAST
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Version Date: 04/20/2023
(Anquil, Glianimon)
Antipsychotic/antieme
tic
Chlorpromazine (Thorazine, Largactil, Megaphen); Droperidol (Inapsine, 
Droleptan, Dridol, Xomolix); Promethazine (Phenergan)
Antipsychotic, atypical Aripiprazole (Abilify, Aripiprex); Asenapine (Saphris, Sycrest); Clozapine 
(Clozaril, Fazaclo, Versacloz); Iloperidone (Fanapt, Fanapta, Zomaril); 
Melperone (Only on Non-US Market) (Bunil, Buronil, Eunerpan); 
Paliperidone (Invega, Xepilon); Pimavanserin (Nuplazid); Risperidone 
(Risperdal); Sertindole (Only on Non-US Market) (Serdolect, Serlect); 
Sulpiride (Only on Non-US Market) (Dogmatil, Dolmatil, Eglonyl, Espiride, 
Modal, Sulpor); Sultopride (Only on Non-US Market) (Barnetil, Barnotil, 
Topral); Zotepine (Only on Non-US Market) (Losizopilon, Lodopin, Setous 
and Zoleptil)
Antiretroviral
Efavirenz (Sustiva and others)
Antisense 
oligonucleotide
Nusinersen (Spinraza)
Antiviral
Rilpivirine (Edurant, Complera, Eviplera); Saquinavir (Invirase [combo])
Beta-3 adrenergic 
antagonist
Mirabegron (Myrbetriq)
Cholinesterase 
inhibitor
Donepezil (Aricept)
Cyclin dependent 
kinase inhibitor
Ribociclib (Kisqali)
Dopamine 2 and 
5HT2a antagonist
Flupentixol (Only on Non-US Market) (Depixol, Fluanxol)
Dopamine agonist
Apomorphine (Apokyn, Ixense, Spontane, Uprima)
Estrogen 
agonist/antagonist
Toremifene (Fareston)
GI stimulant
Cisapride (Removed from Market) (Propulsid)
Glucosylceramide 
synthase inhibitor
Eliglustat (Cerdelga)
Gonadotropin 
receptor 
agonist/antagonist
Leuprolide (Lupron, Eligard, Viadur, Carcinil, Enanton, Leuplin, Lucrin, 
Procren, Prostap and others)
Gonadotropin 
releasing hormone 
agonist/antagonist
Degarelix (Firmagon, Ferring)
Histone deacetylase 
inhibitor
Panobinostat (Farydak); Romidepsin (Istodax); Vorinostat (Zolinza)
Imaging contrast 
agent
Perflutren lipid microspheres (Definity, Optison)


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Imunosuppressant
Tacrolimus (Prograf, Advagraf, Protopic)
Kinase inhibitor
Ceritinib (Zykadia); Crizotinib (Xalkori); Dabrafenib (Tafinlar); Lapatinib 
(Tykerb, Tyverb); Nilotinib (Tasigna); Sunitinib (Sutent); Vemurafenib 
(Zelboraf)
Local anesthetic
Cocaine
Microtubule inhibitor
Eribulin mesylate (Halaven)
Muscle relaxant
Terodiline (Only on Non-US Market) (Micturin, Mictrol [not bethanechol]); 
Tizanidine (Zanaflex, Sirdalud); Tolterodine (Detrol, Detrusitol)
Norepinephrine 
reuptake inhibitor
Atomoxetine (Strattera)
Opioid agonist
Levomethadyl acetate (Removed from Market) (Orlaam); Methadone 
(Dolophine, Symoron, Amidone, Methadose, Physeptone, Heptadon)
Opioid receptor 
modulator
Buprenorphine (Butrans, Belbuca, Bunavail, Buprenex, Suboxone, 
Zubsolv)
Oxytocic
Oxytocin (Pitocin, Syntocinon)
Phosphodiesterase 3 
inhibitor
Anagrelide (Agrylin, Xagrid); Cilostazol (Pletal)
Phosphodiesterase 5 
inhibitor
Vardenafil (Levitra)
Progesterone 
antagonist
Mifepristone (Korlym, Mifeprex)
Proteasome inhibitor
Bortezomib (Velcade, Bortecad)
Psychedelic
Ibogaine (Only on Non-US Market)
Sedative
Dexmedetomidine (Precedex, Dexdor, Dexdomitor)
Selective D2, D3 
dopamine antagonist
Tiapride (Only on Non-US Market) (Tiapridal, Italprid, Sereprile, Tialaread, 
Tiaryl, Tiaprim, Tiaprizal, Sereprid, Tiapridex)
Somatostatin analog
Pasireotide (Signifor)
Sphingosine 
phosphate receptor 
modulator
Fingolimod (Gilenya)
Tyrosine kinase 
inhibitor
Bosutinib (Bosulif); Dasatinib (Sprycel); Osimertinib (Tagrisso); Pazopanib 
(Votrient); Sorafenib (Nexavar)
Vasoconstrictor
Terlipressin (Only on Non US Market) (Teripress, Glypressin, Terlipin, 
Remestyp, Tresil, Teriss and others)
Vasodilator, Coronary Papaverine HCl (Intra-coronary)
Vesicular monoamine 
transporter 2 inhibitor
Deutetrabenazine (Austedo); Valbenazine (Ingrezza); Tetrabenazine 
(Nitoman, Xenazine)


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Version Date: 04/20/2023
Viral protease 
inhibitor
Lopinavir and ritonavir (Kaletra, Aluvia)
Source: CredibleMeds Filtered QT Drug List Rev March 01 2018 (AZCERT.ORG)


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APPENDIX 7. COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS: DIARRHEA (VERSION 5.0)
Definition: A Disorder Characterized by Frequent and Watery Bowel 
Movements.
1
Increase of <4 stools per day over baseline; mild increase in ostomy output compared 
to baseline.
2
Increase of 4 – 6 stools per day over baseline; moderate increase in ostomy output 
compared to baseline; limiting instrumental ADL
3
Increase of >7 stools per day over baseline; hospitalization indicated; severe increase 
in ostomy output compared to baseline; limiting self-care ADL,
4
Life-threatening consequences; urgent intervention indicated.
5
Death


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APPENDIX 8. INVESTIGATOR RESPONSIBILITIES, REQUIRED 
DOCUMENTATION, AND SIGNATURE
Obtain Institutional Review Board (IRB), Research Ethics Board (REB), or Independent 
Ethics Committee (IEC) approval of the protocol and amendments to the protocol and 
Informed Consent Form before initiation of the protocol or any amendments for the study, 
and obtain annual IRB or IEC renewal, as required. Ensure that current FDA and/or ICH-
E6 regulations are followed.
Select all patients per the selection criteria outlined in the study protocol.
Treat and follow patients as described in this research protocol. Complete all electronic 
case report forms (eCRFs) promptly and review eCRFs for accuracy and completeness. 
Provide the original clinical source documents to verify all data entered on eCRFs or SAE 
reports and all data that document the course of the patient throughout their participation 
in the study. Provide a clinical summary to the Sponsor's clinical research monitor.
Report all adverse events to CTI BioPharma Corp. or designee, as required by the protocol.
Ensure that the investigational drug is kept in a secured, limited access area and stored 
under proper conditions. Ensure that all investigational drug receipt and dispensing 
information is recorded and all drug can be accounted for at all times.
Before initiation of the study, each participating investigator will submit to CTI:
-
FDA Form 1572 and, if applicable,
-
Copies of the medical licenses of principal investigators and sub investigators
-
Addresses and descriptions of all clinical laboratory facilities to be used
-
Laboratory certification and expiration dates
-
Normal ranges and effective dates for all required laboratory tests
-
IRB/REB/IEC approval letter referencing the protocol (and amendments, if applicable).
-
IRB/REB/IEC Membership List: A list of the IRB/REB/EC members, their respective 
titles or occupations, and their institutional affiliations.
-
A sample copy of the IRB/REB/IEC-approved Informed Consent Form
-
Curricula vitae: Curricula vitae for the principal investigator and all sub investigators
-
Financial disclosure for the principal investigator and all sub investigators
-
Protocol signature page, signed by the principal investigator
Investigator Statement and Signature
I attest that I have read this protocol, understand and agree to the provisions of the protocol, 
and accept the responsibilities listed above in my role as principal investigator for the study.
Principal Investigator Signature
Date
Principal Investigator Name, Printed


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APPENDIX 9. COMPRESSIVE GERIATRIC ASSESSMENT FORMS 
Please click the below PDF file.
cga.pdf
APPENDIX 10. PILL DIARY
Please click the below Word file.
SUBJECT 
DIARY[75814].docx


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Study Short Title: IIT-Kilari-J31001-BLAST
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Version Date: 04/20/2023
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versus best available therapy for the treatment of myelofibrosis irrespective of baseline 
cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 
2017;4(5):e225-e36.
67.
Verstovsek S, Odenike O, Singer JW, Granston T, Al-Fayoumi S, Deeg HJ. Phase 1/2 
study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid 
malignancies. J Hematol Oncol. 2016;9(1):137.
68.
Jain T, Mesa R. The development, safety and efficacy of pacritinib for the treatment of 
myelofibrosis. Expert Rev Anticancer Ther. 2016;16(11):1101-8.
69.
Bose P, Alfayez M, Verstovsek S. New Concepts of Treatment for Patients with 
Myelofibrosis. Curr Treat Options Oncol. 2019;20(1):5.
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Passamonti F, Maffioli M. The role of JAK2 inhibitors in MPNs 7 years after approval.
Blood. 2018;131(22):2426-35.
71.
Komrokji RS, Seymour JF, Roberts AW, Wadleigh M, To LB, Scherber R, et al. Results 
of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with 
myelofibrosis. Blood. 2015;125(17):2649-55.
72.
Hart S, Goh KC, Novotny-Diermayr V, Tan YC, Madan B, Amalini C, et al. Pacritinib 
(SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. Blood Cancer J. 
2011;1(11):e44.
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Regenbogen T, Chen L, Trinkaus K, Wang-Gillam A, Tan BR, Amin M, et al. Pacritinib to 
inhibit JAK/STAT signaling in refractory metastatic colon and rectal cancer. J Gastrointest 
Oncol. 2017;8(6):985-9.
74.
Gu L MT, Alanen K, Edmonston T, Nevalainen MT. JAK2 V617F Mutation is Absent in 
Advanced Human Prostate Cancers. Cellular Oncology. 2009;In Press, 2010.


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William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, et al. Discovery of the 
macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6). 
1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus 
kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and 
lymphoma. J Med Chem. 2011;54(13):4638-58.
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Van Rompaey L, Galien R, van der Aar EM, Clement-Lacroix P, Nelles L, Smets B, et al. 
Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of 
inflammatory diseases. J Immunol. 2013;191(7):3568-77.
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Nevalainen MT, Harkonen PL, Valve EM, Ping W, Nurmi M, Martikainen PM. Hormone 
regulation of human prostate in organ culture. Cancer Res. 1993;53(21):5199-207.
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Nevalainen MT, Valve EM, Ahonen T, Yagi A, Paranko J, Harkonen PL. Androgen-
dependent expression of prolactin in rat prostate epithelium in vivo and in organ culture. Faseb 
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Nevalainen MT, Valve EM, Ingleton PM, Harkonen PL. Expression and hormone 
regulation of prolactin receptors in rat dorsal and lateral prostate. Endocrinology. 
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Nevalainen MT, Valve EM, Ingleton PM, Nurmi M, Martikainen PM, Harkonen PL. 
Prolactin and prolactin receptors are expressed and functioning in human prostate. J Clin 
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Nevalainen MT, Valve EM, Makela SI, Blauer M, Tuohimaa PJ, Harkonen PL. Estrogen 
and prolactin regulation of rat dorsal and lateral prostate in organ culture. Endocrinology. 
1991;129(2):612-22.
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Maranto C, Udhane V, Hoang DT, Gu L, Alexeev V, Malas K, et al. STAT5A/B Blockade 
Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair. Clin 
Cancer Res. 2018;24(8):1917-31.
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Udhane V, Maranto C, Hoang DT, Gu L, Erickson A, Devi S, et al. Enzalutamide-
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Providing an Exploitable Molecular Target for Jak2 Inhibitors. Mol Cancer Ther. 2020;19(1):231-
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Intermittent androgen suppression for rising PSA level after radiotherapy. The New England 
journal of medicine. 2012;367(10):895-903.

ICF_001.pdf: 
 
Oﬃcial Ɵtle:  PacriƟnib for Biochemical Relapse AŌer DeﬁniƟve Treatment for 
Prostate Cancer 
NCT04635059 
Version date 8/22/2023 – 8/21/2024 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 1 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
Medical College of Wisconsin  
INTRODUCTION TO THE INFORMED CONSENT 
 
IIT-KILARI-J31001-BLAST: A Single-Arm, Open-Label, Phase 2 Study Evaluating PacritiniB for 
Patients with BiochemicaL RelApse after Definitive Treatment for ProStaTe Cancer 
Deepak Kilari, MD 
Department of Medicine 
Medical College of Wisconsin 
8701 Watertown Plank Road 
Milwaukee WI 53226 
414-805-6700 
 
 
 
 
Definitions 
 
Biomarker ± something found in the blood, other fluids, or tissues that can be used to 
measure the progress of disease or how a treatment is working 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 2 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
Purpose 
This project is being done to test the 
effectiveness of a new drug called Pacritinib. 
Researchers would also like to study how 
Pacritinib slows down the time until cancer 
progression and assess its safety and 
tolerability. 
Length 
1. You will be in this research project for 
about 2 years.  
 We would also like to follow you for every 
6 months for 2 years to monitor how you 
are doing. 
Risks 
This is a brief list of the most commonly seen 
side effects. The full consent form after this 
introduction contains a more complete list of 
potential research risks. 
Pacritinib risks: 
 
Gastrointestinal side effects such as 
diarrhea (loose, watery stools), 
nausea, vomiting 
 
General side effects such as fatigue 
(feeling very tired), fever, and swelling 
of limbs (peripheral edema) 
 
Decreased amounts of red blood cells 
(anemia), platelet cells 
(thrombocytopenia), and white blood 
cells (neutropenia) 
 
Abnormal blood cell counts 
(leukopenia) and fever associated with 
low white blood cell count (febrile 
neutropenia) 
 
Bleeding in the throat (pharyngeal 
hemorrhage), digestive tract 
(esophageal varices hemorrhage), 
brain (cerebral hemorrhage and 
subdural hematoma), stroke 
(cerebrovascular accident), and 
nosebleeds (epistaxis) 
 
Abnormal heart rhythm (prolonged QT, 
bradycardia, cardiac fibrillation, sinus 
tachycardia, and atrioventricular [A-V] 
block) 
 
Cardiac and vascular conditions 
(angina pectoris, myocardial ischemia, 
hypertensive crisis), cardiac 
inflammation (pericarditis), heart attack 
(myocardial infarction), and cardiac 
failure (including congestive heart 
failure) 
Procedures 
All subjects in this study will be treated with 
Pacritinib. Pacritinib will be administered in 
28-day cycles. 
 
List of visits: 
 
Screening Visit(s) 
- Total Number: approx. 1-3 
- Total Time: approx. 6-12 hours 
 
Treatment Visits 
- Total Number: until your cancer 
progresses 
- Total Time: approx. 2-4 hours each 
 
End of Treatment Visit(s) 
- Total Number: approx. 1-2 
- Total Time: approx. 2-3 hours 
 
Procedures that will occur at various 
visits: 
 
Invasive Procedures 
- Blood collection for routine 
laboratory tests and research tests 
- Tumor assessments by 
CT/MRI/Bone scan 
 
Non-invasive Procedures 
- Physical exam and vital signs 
- Heart monitoring by 
Electrocardiogram (ECG) and 
Echocardiogram (ECHO) 
- Performance Status 
- Quality of Life questionnaires 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 3 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
My Other Options 
You do not have to join this project. Your other 
options may include: 
1. Joining a different project 
2. Routine care for this condition  
3. Getting no treatment for this condition 
 
Benefits 
We don¶t know if this project will help you. Your 
condition may get better but it could stay the 
same or even get worse. 
If you have more questions about this project at any time, you can call Deepak Kilari, MD at 
414-805-6700 
 
If you have questions about your rights as a participant, want to report any problems or 
complaints, or offer input, you can call the MCW/Froedtert Hospital Research Subject 
Advocate at 414-955-8844. 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 4 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
CONSENT TO PARTICIPATE IN RESEARCH 
A1. INTRODUCTION ± WHY ARE WE ASKING YOU TO PARTICIPATE? 
You are being invited to participate in this research because you have prostate adenocarcinoma 
that has recurred (come back again) after a radical prostatectomy surgery or radiation therapy. 
 
A total of about 46 people are expected to participate in this research at the Medical College of 
Wisconsin/Froedtert Hospital. 
 
The Director of the project is Deepak Kilari, MD in the Department of Medicine. A research team 
works with Dr. Kilari. You can ask who these people are.  
 
CTI BioPharma, a pharmaceutical company that produces the study drug Pacritinib, is funding 
this study. The study is also being funding by Cancer Center funds. 
 
A2. DO I HAVE TO PARTICIPATE? 
You can decide whether to take part in this research or not. You are free to say yes or no. If you 
do not agree to join, or if you leave, you will not be penalized or lose any benefits that you had 
before starting the research project. Even if you join this project, you do not have to stay in it. 
You may stop at any time. Take as much time as you need to make your choice.  
 
A research project is different from routine medical care in three ways: 1) there are extra risks 
that we will tell you about in this form; 2) you may have some extra medical tests and visits; 3) 
the research procedures, tests and visits follow a set plan that must be kept. 
 
A3. WHY IS THIS PROJECT BEING DONE? 
The most common standard of care treatment for recurrent prostate cancer, Androgen 
Deprivation Therapy (ADT), tries to slow down the growth of cancer cells by reducing the level 
of male hormones. However, there are many common side effects associated with these drugs 
due to resulting lower levels of testosterone in the body. Patients treated with ADT report lower 
quality of life because of the side effects. Current standard of care treatment is usually 
continued for life, so it is a priority to develop new prostate cancer therapy options with fewer 
side effects. 
 
The purpose of this study is to test the effectiveness of a new drug called Pacritinib. 
Researchers would also like to study how Pacritinib slows down the time until cancer 
progression. They would also like to assess the safety and toxicity of Pacritinib and see how it 
compares with standard of care treatments. Pacritinib is investigational in this study, meaning it 
has not been approved by the FDA for the treatment of prostate cancer. In addition, although 
Pacritinib has been studied to treat other cancers, it has not previously been tested in other 
clinical trials as a treatment for prostate cancer. 
 
We don¶t know if this study will help you. Your condition may get better, but it could stay the 
same or even get worse. We hope the information from this study will help us develop a better 
treatment for prostate cancer in the future. 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 5 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
B1. WHAT WILL HAPPEN IF I PARTICIPATE? 
STUDY DRUG 
If you participate in the study, Pacritinib will be taken orally (by mouth) as a capsule. The 
capsules should not be opened or crushed. If the capsule if crushed or damaged, you should 
not touch the powder inside the capsule as it may irritate the skin or mucous membranes (e.g. 
inside of the nose). You should store Pacritinib capsules at room temperature. 
Pacritinib will be administered in 28-day cycles. You will take two 100 mg Pacritinib capsules 
(200 mg Pacritinib in each dose) twice daily, for a total of 400 mg each day. The two doses 
should be taken about 12 hours apart. You will be asked to complete a Subject Diary to record 
when you take each dose of Pacritinib and any side effects you may experience. You will return 
to the clinic at the beginning of each cycle to receive an additional supply of Pacritinib. You 
should bring any remaining Pacritinib capsules and the Subject Diary with you to all study visits. 
 
STUDY GROUP 
 
All subjects in this study will be treated with Pacritinib. The study is open label, meaning you, 
your study doctor, and other members of the study team will know your treatment. 
 
STUDY VISITS 
 
Screening  
If you agree to participate in the study, you will sign this consent form before screening 
assessments are performed to see if you are eligible. Your study doctor or a member of the 
study team will let you know if you are eligible to participate in the study. If you are unable to 
participate in the study, the study doctor will discuss other treatment options with you.  
 
Treatment  
If you are eligible to participate, you will begin Pacritinib treatment as described above. You will 
return to the clinic on Day 1 and Day 15 during Cycle 1, on Day 1 during Cycles 2-5, and then 
every other cycle from Cycle 6 and beyond. Assessments to track your disease status and to 
monitor you for side effects will occur during the treatment visits. You will continue Pacritinib 
treatment about 2 years. If your study doctor thinks that you may benefit from continued 
Pacritinib treatment beyond 2 years, the treatment period may be extended. 
 
Follow-up  
After you stop Pacritinib treatment, you will return to the clinic 30 days after your last dose for an 
End of Treatment visit to monitor for any side effects of the study drug. You will then return to 
the clinic every 6 months for 2 years to monitor how you are doing. 
 
STUDY ASSESSMENTS 
 
Screening 
You will need to have all or some of the following exams, tests, or procedures to find out if you 
can be in the study. Some of them are routine and may be done even if you do not join the 
study. If some of the tests were completed recently, they may not have to be repeated. 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 6 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
 
Informed consent: Prior to any study-related procedures being performed, you will be 
required to voluntarily sign and date this consent form. 
 
Medical history: You will be asked about your health status, including previous 
treatments for your cancer, and demographic information 
 
Medications: You will be asked about your current medications, including over-the-
counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Electrocardiogram (ECG) and Echocardiogram (ECHO): ECG and ECHO will be 
performed to check the activity of your heart 
 
Blood tests: Blood samples will be collected for 
o PSA and testosterone levels 
o Blood cell counts, blood chemistry, clotting ability, and organ function 
 
CT/MRI/PET/Bone scan: You will have a tumor assessment by CT, MRI, PET, and/or 
bone scan to assess the size and location of cancer 
 
FACT-P Quality of Life and Comprehensive Geriatric Assessment questionnaires: 
Questions about daily activities and mental, physical, and emotional symptoms, etc. 
 
Treatment 
You will begin Pacritinib treatment if the results of screening assessments show that you are 
eligible. 
 
Cycle 1 Day 1 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Electrocardiogram (ECG): ECG will be performed to check the activity of your heart 
 
Blood tests: Blood samples will be collected for 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 7 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
o PSA level
o Blood cell counts, blood chemistry, and organ function 
 
Cycle 1 Day 15 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Blood tests: Blood samples will be collected for 
o Blood cell counts, blood chemistry, and organ function 
 
Cycle 2 Day 1 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Electrocardiogram (ECG) and Echocardiogram (ECHO): ECG and ECHO will be 
performed to check the activity of your heart 
 
Blood tests: Blood samples will be collected for 
o PSA level 
o Blood cell counts, blood chemistry, and organ function 
 
Cycle 3 Day 1 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 8 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Blood tests: Blood samples will be collected for 
o PSA level 
o Blood cell counts 
 
Cycle 4 Day 1 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Blood tests: Blood samples will be collected for 
o PSA and testosterone levels 
o Blood cell counts 
 
CT/MRI/PET/Bone scan: You will have a tumor assessment by CT, MRI, PET, and/or 
bone scan to assess the size and location of cancer 
 
FACT-P Quality of Life and Comprehensive Geriatric Assessment questionnaires: 
Questions about daily activities and mental, physical, and emotional symptoms, etc. 
 
Cycle 5 Day 1 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 9 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
 
Electrocardiogram (ECG) and Echocardiogram (ECHO): ECG and ECHO will be 
performed to check the activity of your heart 
 
Blood tests: Blood samples will be collected for 
o PSA level 
o Blood cell counts 
 
Cycle 6 and beyond 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Electrocardiogram (ECG) and Echocardiogram (ECHO): ECG and ECHO will be 
performed to check the activity of your heart. ECG will be performed every 4 months. 
ECHO will be performed every 6 months. 
 
Blood tests: Blood samples will be collected for 
o PSA level 
o Blood cell counts and blood chemistry 
 
At progression 
The following assessments will be performed: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Blood tests: Blood samples will be collected for 
o PSA level 
o Blood cell counts, blood chemistry, and organ function 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 10 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
 
CT/MRI/PET/Bone scan: You will have a tumor assessment by CT, MRI, PET, and/or 
bone scan to assess the size and location of cancer 
 
FACT-P Quality of Life questionnaire: Questions about daily activities and mental, 
physical, and emotional symptoms, etc. 
 
Follow-up 
End of Treatment Visit 
The following assessments will be performed 30 days after you stop Pacritinib treatment: 
 
Adverse events: You will be asked about if you experienced any changes in your health 
 
Medications: You will be asked about any changes in your current medications, including 
over-the-counter medications, vitamins, and herbal supplements 
 
Physical examination: You will receive a complete physical examination 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, temperature, and weight will 
be checked 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Blood tests: Blood samples will be collected for 
o PSA level 
o Blood cell counts, blood chemistry, and organ function 
 
Follow-up Visits 
You will return to the clinic every 6 months for 2 years to monitor your health. The following 
assessments will be performed at each Follow-up Visit: 
 
Physical examination: You will receive a complete physical examination 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Blood tests: Blood samples will be collected for 
o PSA level 
 
SAMPLES FOR RESEARCH 
 
You will be asked to provide the following samples to be used for biomarker research: 
 
Tumor tissue 
 
Archival tissue from previous biopsies, if sufficient tissue is available 
 
Blood samples 
 
Cycle 1 Day 1 
 
Cycle 2 Day 1 
 
Cycle 4 Day 1 
 
At time of progression 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 11 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
EFFECTIVE 
 
8/22/2023 
 
MCW IRB
The samples will be used to analyze different biomarkers. A biomarker is something found in the 
blood, other fluids, or tissues that can be used to measure the progress of disease or how a 
treatment is working. This future research will be related to this current study. Allowing your 
tumor tissue and blood samples to be used for biomarker research is optional. You may still 
participate in the study even if you do not allow your samples to be used for biomarker research. 
I agree that my tumor tissue and blood samples can be used for 
biomarker research  
 
Yes              No 
 
GENETIC TESTING 
In this study, we will do genetic testing on your biospecimens. Whole genome sequencing may 
be included as part of the genetic testing for this research. This will be collected at the visits 
listed in the ³SAMPLES FOR RESEARCH´ heading above. Genetic testing will be done 
because researchers would like to better understand how genes affect health and response to 
treatment. 
 
This genetic testing is for research only. The purpose is not to discover information that could be 
used to change your medical care, make or change your diagnosis, or advise you on your risk of 
diseases. 
 
The biospecimens collected for this part of the study will be coded, which means they will be 
labeled with numbers and/or letters instead of information that could identify you. Only the 
research team will be able to link the code to you. The samples will also be labeled with date of 
collection, which could potentially be used to identify you. The research team will make every 
effort to protect the information and keep it confidential, but it is possible that an unauthorized 
person might see it. Depending on the kind of information being collected, it might be used in a 
way that could embarrass you.  
 
It is against federal law (Genetic Information Nondiscrimination Act, or GINA) for health 
insurance companies to deny health insurance, or large employers to deny jobs, based on your 
genetic information. But the same law does not protect your ability to get disability, life, or long-
term care insurance. If you have questions, you can talk to the research doctor about whether 
this could apply to you. 
 
You will not be given your genetic test results. 
 
B2. HOW LONG WILL I BE IN THE PROJECT? 
You will continue Pacritinib treatment for about 2 years. If your study doctor thinks that you may 
benefit from continued Pacritinib treatment beyond 2 years, the treatment period may be 
extended. 
 
After you stop Pacritinib treatment, you will return to the clinic 30 days after your last dose for an 
End of Treatment visit to monitor for any side effects of the study drug. You will then return to 
the clinic every 6 months for 2 years to monitor how you are doing. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
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B3. CAN I STOP BEING IN THE PROJECT?   
You are free to withdraw from the project at any time. If you leave, your regular medical care will 
not change. If you are thinking about leaving, please tell the research doctor.  
The research doctor can tell you about the effects of stopping, and you and the research doctor 
can talk about what follow-up care would help you the most. 
You might be asked to come back for follow-up visit(s) to check your health. 
You might be asked to return your research drug containers. 
The research doctor may take you out of this project at any time. This would happen if: 
 
They think it is in your best interest. 
 
You do not follow the project rules. 
 
The whole project is stopped. 
 
If this happens, the research doctor will tell you. 
B4. ARE THERE ANY SPECIAL INSTRUCTIONS WHILE I AM IN THE PROJECT?  
You should tell the study doctor of any changes in your current medications, including over-the-
counter medications, vitamins, and herbal supplements. Some medications are not allowed 
during the study. Your study doctor will advise about which medications these are. 
 
You should bring remaining study drug and the Subject Diary to all treatment visits. 
 
C1. WHAT HEALTH RISKS OR PROBLEMS CAN I EXPECT FROM THE PROJECT? 
There are risks to taking part in any research project. There is a risk that you may get a drug 
that does not help your condition or may make it worse.  There also may be problems (side 
effects) we do not know about yet, from the drug itself, or how it combines with other drugs you 
are taking. If we learn about new important side effects, we will tell you.  
 
We watch everyone in the project for problems (side effects). You need to tell the research 
doctor or a member of the research team immediately if you experience any problems, 
side effects, or changes in your health. In an emergency, call 911. 
 
C2. RISKS OF PACRITINIB 
The research drug itself may cause problems (side effects).  Side effects may be mild or very 
serious.  Some can last a long time or never go away.   
 
Pacritinib has been given to approximately 1128 patients in 16 completed studies. Based on the 
adverse effects reported from the completed studies, the main identified risks for Pacritinib 
included gastrointestinal events, bleeding, and cardiac events. 
 
Life-threatening and sometimes fatal cardiac events have been observed in participants 
treated with Pacritinib, including heart failure and arrhythmias, some of which may have 
been associated with sudden death. 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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Serious bleeding events, specifically bleeding of the brain (intracranial hemorrhage, 
subdural hematoma, and cerebral hemorrhage), have been observed in association with 
Pacritinib treatment occasionally with life-threatening or fatal outcomes.  
Very common side effects occurring in at least 10% of participants who received Pacritinib 
include:  
 
Gastrointestinal side effects such as diarrhea (loose, watery stools), nausea, vomiting 
 
General side effects such as fatigue (feeling very tired), fever, and swelling of limbs 
(peripheral edema) 
 
Decreased amounts of red blood cells (anemia), platelet cells (thrombocytopenia), and 
white blood cells (neutropenia) 
 
Common side effects occurring in 1% to 10% of those who received Pacritinib include: 
 
Abnormal blood cell counts (leukopenia) and fever associated with low white blood cell 
count (febrile neutropenia) 
 
Bleeding in the throat (pharyngeal hemorrhage), digestive tract (esophageal varices 
hemorrhage), 
brain 
(cerebral 
hemorrhage 
and 
subdural 
hematoma), 
stroke 
(cerebrovascular accident), and nosebleeds (epistaxis) 
 
Abnormal heart rhythm (prolonged QT, bradycardia, cardiac fibrillation, sinus tachycardia, 
and atrioventricular [A-V] block) 
 
Cardiac and vascular conditions (angina pectoris, myocardial ischemia, hypertensive 
crisis), cardiac inflammation (pericarditis), heart attack (myocardial infarction), and cardiac 
failure (including congestive heart failure) 
 
Gastrointestinal effects including abdominal pain, fluid in abdomen, poor appetite, 
dehydration, and weight changes 
 
Cancers of skin 
 
Changes in laboratory results such as elevated bilirubin in the blood, increased liver 
enzymes (indicating liver damage), high levels of uric acid in the blood (hyperuricemia and 
gout), abnormal blood glucose (including diabetes mellitus), and electrolyte changes 
 
General effects such as shortness of breath, weakness (including muscles), numbness 
and pain of limbs, headache, low blood pressure, dizziness and vertigo, syncope, and fall 
 
Kidney and bladder disorders including kidney failure and kidney stones 
 
Reproductive tract disorders such as inflammation of testes (orchitis and epididymitis) 
 
Skin disorders (rash and itching) 
 
Infections including abscess, gastroenteritis, pneumonia, bronchitis, and urinary tract 
infection 
 
Uncommon side effects occurring in less than 1% of participants who received Pacritinib which 
could be potentially life-threatening include:  
 
Pulmonary conditions (pulmonary arterial hypertension, pulmonary embolism, pulmonary 
infarction, and interstitial lung disease) and other respiratory effects (fluid in lungs, acute 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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Protocol Version: V3 v. 4/20/23 
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respiratory distress syndrome, and respiratory failure) 
 
Severe infections (bacterial/viral/fungal, with possible sepsis, shock, and organ failure) 
 
Digestive tract disorders (diverticular perforation - diverticula are small, bulging pouches 
that can form in the lining of your digestive system; most often found in the lower part of 
the large intestine) and hepatic disorders (portal hypertension - an increase in the 
pressure within the portal vein (the vein that carries blood from the digestive organs to 
the liver). The increase in pressure is caused by a blockage in the blood flow through the 
liver. 
 
Transformation into Acute Myeloid Leukemia (AML) 
 
Ask the study doctor or study staff if you have questions about the signs or symptoms of any side 
effects you read about in this consent form.
 
Could I have an allergic reaction?
Sometimes people have allergic reactions to drugs.  If you have a very bad allergic reaction, you 
could die.  Some things that happen during an allergic reaction that could be a sign or symptom 
of a life-threatening allergic reaction (anaphylaxis) are: 
 
A rash or hives 
 
Having a hard time breathing 
 
Wheezing when you breath 
 
A sudden drop in blood pressure (making you feel dizzy or lightheaded) 
 
Swelling around the mouth, throat, or eyes 
 
A fast pulse 
 
Sweating 
 
You should get immediate medical help and contact the study doctor or study staff if you have 
any of these or any other side effects during the study. 
 
C3. OTHER RISKS OF THIS RESEARCH PROJECT 
Other procedures that are part of the research also involve some risks: 
 
Electrocardiogram (ECG) 
An ECG procedure requires you to lie still for a few minutes while electrodes are attached to 
your chest, wrists, and ankles to record the activity of your heart. The ECG leads placed on your 
skin may cause slight discomfort during their placement and removal. 
 
Echocardiogram (ECHO) 
During the echocardiogram, electrodes will be placed onto your chest to allow for an ECG to be 
performed.  Then a transducer (a device that looks like a computer mouse) will be applied.  You 
may feel slight pressure on your chest from the transducer.  In addition, you may be asked to 
breathe in a certain way or to rest on your side during the test. 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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Blood collection 
Blood collection may cause some discomfort, bleeding, or bruising at the puncture site. A small 
blood crust or swelling may occur at this site. In rare cases, fainting or local infection may occur. 
If you feel discomfort during blood collection, please report this to the study doctor or staff at the 
time. 
Computed Tomography (CT Scan) 
CT scans use x-rays to create an image. If frequent CT scans are performed, the cumulative 
amount of radiation involved could be concerning. The mean effective dose from a diagnostic 
abdomen and pelvis CT procedure is around 10 mSv, which is equivalent to natural background 
radiation for around 3 years. People who have a small but increased radiation exposure may 
have the risk of cancer development in later life. However, there is considerable uncertainty 
regarding the risk estimates for low levels of radiation exposure from the CT scans you will 
undergo. 
 
Magnetic Resonance Imaging (MRI Scan) 
MRI, which uses a large magnet instead of x-rays to take pictures of your body, you may feel 
mild vibrations throughout your body. The machine will produce a loud knocking noise. This is 
normal. You will be given earplugs to protect your ears. Some people, especially those who 
tend to feel uncomfortable in small or closed spaces, may feel ³closed in´ and become anxious 
while in the scanner. The scanner has an intercom, which will allow you to speak to the staff 
during the procedure. If you feel ill or anxious during scanning, tell the MRI staff and the 
scanning will be stopped if you wish. 
 
The MRI will require a catheter to be inserted into one of your veins in order to inject the MRI 
contrast agent. This may cause skin irritation, bleeding, and/or infection. You may have an 
allergic reaction to the contrast agent.  
 
The magnetic field used in MRI scanning may harm people who have metal in their bodies 
(pacemakers, neurostimulators, certain clips, or staples from surgery). It may cause problems 
with devices, such as pacemakers. If you have metal in your body or a pacemaker, you should 
not have an MRI. Your study doctor will discuss with you whether you should have a MRI scan 
with a contrast agent based on your health status. 
 
Bone scan 
During a bone scan, a radioactive substance called a tracer is injected into a vein. The tracer 
travels through your bloodstream and into your bones. The tracers in the radioactive dye used in 
a bone scan produce very little radiation exposure. Then a special camera takes pictures of the 
tracer in your bones. Areas that absorb little or no amount of tracer appear as dark or µcold¶ 
spots, while areas that concentrate the tracer appear as µhot¶ spots. 
 
PET-CT 
Positron emission tomography (PET) is a type of imaging test that uses a small amount of 
radioactive material injected into your vein to see how cells or tissues are functioning. Before 
the scan, you will have to follow preparation instructions including not eating for 6 hours before 
the test. After the PET agent is injected, you will wait 45-60 minutes before being scanned. The 
scan will take several minutes, and you must lie still during that time. 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
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Risks of Questions on Your Well-Being 
The answers that you give are confidential, but there is always a risk that your answers will be 
read by people who should not read your personal information. You may also feel 
uncomfortable answering some of the questions. 
Privacy and Confidentiality 
Another risk may be loss of confidentiality. Every effort will be made to keep your research 
records confidential but we cannot guarantee it. Depending on the kind of information being 
collected, if your research information were accidentally seen, it might be used in a way that 
could embarrass you or affect your ability to get insurance. If you have questions, you can talk 
to the project director about whether this could apply to you. 
C4. REPRODUCTIVE RISKS 
Risks to a subject¶s partner(s) 
If you and your partner(s) are able to become pregnant, one or both of you must use some form 
of effective birth control, because it is unknown if the study drug could affect a baby. You must 
tell the research doctor right away if you think your partner is pregnant. 
 
You may not donate sperm during your participation in the project or for 90 days after stopping 
the study drug. 
 
Birth control methods for all subjects 
Check with the research doctor about the birth control methods needed for this project and how 
long to use them. Some methods might not be good enough for this project. If you are having 
sex that could lead to pregnancy, you should use two forms of highly effective birth control while 
you are in this project.   
 
This may include: 
 
Not having vaginal sex (abstinence) 
 
Taking birth control pills orally 
 
Having birth control shots or patches such as Depo-Provera 
 
Surgical sterilization (hysterectomy/tubal ligation or vasectomy) 
 
Limiting sexual activity to a partner who has undergone surgical sterilization  
 
Use of an intrauterine device (IUD) 
 
Use of diaphragm with contraceptive jelly 
 
Use of condoms with contraceptive foam 
 
Use of diaphragm with condoms (³double barrier´) 
 
You should continue using birth control for 90 days after stopping the study drug. 
 
C5. ARE THERE ANY BENEFITS TO TAKING PART IN THE PROJECT? 
We don¶t know if this study will help you. Your condition may get better but it could stay the 
same or even get worse. We hope the information from this study will help us develop better 
treatments for prostate cancer. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
Page 17 of 21 
Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
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D1. ARE THERE ANY COSTS TO BEING IN THE PROJECT? 
Most of the medical care that you will receive in this project is considered routine care for your 
condition and would be recommended whether or not you join the project.  Costs for routine 
care will be billed to you or your insurance carrier. For routine clinical care, you will be 
responsible for paying any copayment, coinsurance, or deductible that is required by your 
insurance carrier.  
Activities / costs that are part of the project will not be billed to you or your insurance company. 
These are: 
 
Study drug (Pacritinib) 
 
Heartbeat tests (ECG, ECHO/TTE)  
 
Coagulation tests (PT/PTT/HbA1C) 
 
Cholesterol 
 
Collection, processing, and analysis of research specimens (tissue, blood) 
 
Any screening procedure if repeated 
 
Some insurers will not pay for drugs, tests or hospitalization that are part of research, so check 
with your insurer before you join this project. If you have questions regarding costs, please 
contact Dr. Kilari. 
 
If you participate in this research, the costs of any necessary emergency medical treatment in 
the event of a research-related injury will be billed to you or your health insurance. 
 
D2. WILL I BE PAID FOR PARTICIPATING IN THE PROJECT? 
There is no payment for being in this project. 
 
Sponsor, other researchers, or research companies may patent or sell products, discoveries 
and data or information that result from this research. Neither Sponsor nor Dr. Kilari will pay you 
if this happens. You will not receive any payment or commercial rights for products, data, 
discoveries, or materials gained or produced from your health information/biospecimens. 
 
D3. WHAT OTHER HEALTHCARE CHOICES DO I HAVE? 
You do not have to join this project. You are free to say yes or no. If you do not join this project, 
your research doctor can discuss other healthcare choices with you.  
 
Your other choices may include: 
 
Routine care for this condition or symptoms. 
 
Joining a different research project 
 
The procedure or drug offered to you may also be available without being in any 
research project. 
 
The research doctor can explain both the possible benefits and the risks of other options that 
are available to you. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
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D4. WILL I BE GIVEN NEW INFORMATION ABOUT THE PROJECT? 
If we learn any important new information about the drug that might change your mind about 
being in the project, we will tell you about it right away.  You can then decide if you want to stay 
in the project. 
 
When research biospecimens are collected and analyzed, there is the chance of finding 
something clinically relevant. There may be benefits to learning such results (such as early 
detection and treatment of a medical condition), but there are risks as well (such as feeling 
worried about a finding for which no treatment is required or appropriate). 
The results from the biospecimens we collect in this research study are not the same quality as 
what you would receive as part of your health care, so you will not be informed of any clinically 
relevant research findings. The results of your research biospecimens will not be placed in your 
medical record. 
D5. WHAT HAPPENS IF I AM INJURED BECAUSE I TOOK PART IN THE PROJECT?  
Emergency medical treatment for injuries directly related to your participation in this research 
project will be provided to you. You or your health insurance will be billed for the costs of this 
emergency treatment.  MCW will decide on a case by case basis if they will reimburse you or 
your insurer for emergency treatment costs.  If your research-related injury requires medical 
care beyond this emergency treatment, you or your insurer will be responsible for the costs of 
this follow-up care.  
At this time, there is no plan for any additional financial payments. 
If you believe that you have been injured because of your participation in this project, contact 
the research doctors right away.  Contact information: Deepak Kilari, 414-805-6700  
 
Nothing in this consent form affects any legal rights you may have nor does it release the 
investigator, the sponsor, the institution, or its agents from liability for negligence. 
 
D6. WHO CAN ANSWER MY QUESTIONS ABOUT THE PROJECT? 
- 
If you have more questions about this project at any time, you can call Deepak Kilari, MD 
at 414-805-6700. 
- 
If you have questions about your rights as a research participant, want to report any 
problems or complaints, or offer input, you can call the MCW/Froedtert Hospital Research 
Subject Advocate at 414-955-8844. 
 
E. PERMISSION TO COLLECT, USE AND SHARE HEALTH INFORMATION 
E1. What health information will be collected and used for this project? 
To be in this research project, the research team needs your permission to access, collect and 
use some of your health information. If you say no, you cannot be in the project. This 
information may come from questions we ask, forms we ask you to fill out, or your medical 
record, as described below. We will only collect and use information needed for the project. 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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The protected health information (PHI) originates from services you will or have received at one 
or more of the following locations: the Medical College of Wisconsin (MCW); Versiti, Inc.; 
Children¶s Hospital of Wisconsin (CHW); any Froedtert Health Affiliate- Froedtert Hospital (FH), 
Inc.; Froedtert Menomonee Falls Hospital;  Froedtert West Bend Hospital;  Froedtert & The 
Medical College of Wisconsin Community Physicians Clinics, Inc. (FMCWCP); the West Bend 
Surgery Center, LLC; and the Froedtert Surgery Center, LLC.  
The health information to be collected and used for this project is:
 
Past and present medical records to document relevant preexisting conditions 
 
Records about your study visits and results of tests done during the study 
 
Records about phone calls made as part of this research 
 
Research records 
 
E2. Who will see the health information collected for this project? 
The only MCW/Froedtert Hospital. employees allowed to handle your health information are 
those on the research team, those on the Institutional Review Board (IRB) and those who check 
on the research activities to make sure the hospital¶s rules are followed. 
 
If the costs of any necessary emergency medical treatment in the event of a research-related 
injury are billed to your health insurance, your health information may need to be disclosed to 
the insurer for billing purposes. 
 
The research team may share your information with people who don¶t work at MCW/Froedtert 
Hospital because they planned, pay for, or work with us on this project.  The federal Privacy 
Rule may no longer protect your health information once it leaves MCW/Froedtert Hospital.  For 
this project, we plan to share information with those doctors, researchers or government 
representatives working with us on this project at the institutions or companies listed here: 
 
 
The pharmaceutical company providing study drug, CTI Biopharma, and its research 
partners; 
 
Government agencies in the U.S., such as the Food and Drug Administration (FDA), 
National Cancer Institute (NCI), and National Institutes of Health (NIH); 
 
Other federal and state agencies, such as the Office of Human Research Protections, 
(OHRP); 
 
Others required by law 
 
Florence Healthcare, Inc. 
 
Because this project involves the use of drugs and/or devices, the FDA also has the right to 
inspect all project records. 
 
We may record your research information, including results of tests and procedures done for 
research, in your Froedtert Hospital and/or Medical College of Wisconsin medical record.  As a 
result, this research information may be seen by people allowed to see your medical records for 
healthcare operations or treatment, by those you allow to see your medical records by giving 
written permission, and by others when required by law. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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Protocol Version: V3 v. 4/20/23 
ICF Version: 4/5/23 
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We will not use your personal health information for a different project without your permission 
or the permission of a hospital research review board (IRB). Once all personal identification is 
removed from your health information and/or biospecimens, the information and/or 
biospecimens may be used for future research or distributed to another investigator for future 
research without additional informed consent from you or your legally authorized representative. 
The information might also be used or released for other purposes without asking you. Results 
of the project may be presented in public talks or written articles, but no information will be 
presented that identifies you. 
 
E3. What are the risks of sharing this health information? 
One risk of taking part in a research project is that more people will handle your personal health 
information collected for this project. The research team will make every effort to protect the 
information and keep it confidential, but it is possible that an unauthorized person might see it. If 
you have questions, you can talk to the research doctor about whether this could apply to you.  
 
E4. How long will you keep the health information for this project? 
If you sign this form, we plan to keep your information without any end-date in case we need to 
check it again for this project. 
 
E5. Can I cancel my permission to share this health information? 
If you change your mind later and do not want us to collect or share your health information, you 
need to send a letter to Deepak Kilari, MD at  
 
Department of Medicine 
Medical College of Wisconsin 
8701 Watertown Plank Road 
Milwaukee WI 53226 
 
The letter must say that you have changed your mind and do not want the researcher to collect 
and share your health information. At that time, we will decide that you cannot continue to be 
part of the project. We may still use the information we have already collected. 
 
E6. Access to records 
You may not be able to see, or copy, your project-related health information until after the 
project has been completed; otherwise, it could affect the study.   
 
F1. FOR MORE INFORMATION ABOUT THE PROJECT
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
You can look up this project by referring to the ClinicalTrials.gov number (NCT04635059) or by 
asking the research team for a printed copy.    


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: November 1, 2019 
IRB Protocol Number: PRO 40162 
IRB Approval Period: 8/22/2023 ± 8/21/2024
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Protocol Version: V3 v. 4/20/23 
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CONSENT TO PARTICIPATE 
By signing my name below, I confirm the following: 
 
I have read (or had read to me) this entire consent document.  
All of my questions have been answered to my satisfaction. 
 
The project¶s purpose, procedures, risks and possible benefits have been explained to me.   
 
I agree to let the research team use and share the health information and other information 
gathered for this project. 
 
I voluntarily agree to participate in this research project. I agree to follow the procedures as 
directed. I have been told that I can stop at any time. 
IMPORTANT: You will receive a signed and dated copy of this consent form.  Please keep it 
where you can find it easily.  It will help you remember what we discussed today. 
 
 
 
 
Subject's Name please print  
Subject's Signature 
Date    
 
 
 
Name of Witness, if applicable 
please print 
Signature of Witness 
 
Date 
Rationale for Use of Witness 
 Subject has limited/no literacy 
 Subject has limited English 
proficiency 
 Subject has limited/no vision
 
 Sponsor requirement 
 Other 
____________________ 
 
 
 
 
 
* Name of person discussing/ 
obtaining consent please print  
Signature of person 
discussing/obtaining consent 
Date 
* A member of the research team trained and authorized by the Principal Investigator to act on 
her/his behalf in obtaining informed consent according to the protocol.  The Principal 
Investigator is responsible and accountable for the research project.