Clinical trial NCT03627403
Conditions: Primary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Post-polycythemia Vera Myelofibrosis
Sponsor: University of Utah
Start date: 2019-05-10; Completion date: 2025-03-05
Enrollment: 17 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase II, open label, prospective, single-arm study evaluating the efficacy and safety of selinexor in patients with PMF or secondary MF (PPV-MF or PET-MF) who are refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.

Detailed description:

Arms: arm 1: Single Arm Study, all patients will get selinexor
Interventions: intervention 1: Selinexor
Intervention descriptions: intervention 1: Selinexor will be administered orally at a dose of 80 mg once weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first.

For patients enrolled after Protocol v7, Selinexor will be administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of sSelinexor was 60 mg and 80 mg once weekly.

Protocol documents:
Prot_SAP_000.pdf: 
Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Principal Investigator: Srinivas Tantravahi, MBBS, MRCP 
A Phase II Study to Evaluate the Efficacy and Safety of Selinexor in 
Patients with Myelofibrosis Refractory or Intolerant to JAK1/2 
Inhibitors (ESSENTIAL) 
CTO # HCI-17-HEM-13 – IRB # 114354 
Principal Investigator 
(Sponsor-Investigator) 
Srinivas Tantravahi, MBBS, MRCP 
Huntsman Cancer Institute - University of Utah 
2000 Circle of Hope 
Salt Lake City, UT 84112 
Phone: 801-213-6170 
Email: Srinivas.Tantravahi@hci.utah.edu 
Statistician 
Kenneth M. Boucher, PhD 
Statistician 
Research Associate Professor, Internal Medicine  
Huntsman Cancer Institute - University of Utah 
2000 Circle of Hope Room 1710 
Email: Kenneth.Boucher@hci.utah.edu 
DSMC Medical Monitor 
Paul Shami, MD 
Sponsor 
 
Drug Manufacturer and 
Funding Source 
Huntsman Cancer Institute – University of Utah 
 
Karyopharm Therapeutics, Inc.  
85 Wells Avenue 
Newton, MA 02459 USA 
Tel. + (617) 658-0600 
Drug Manufacturer IST 
Protocol Identifier 
IST-302 
Investigational agent 
Selinexor (KPT-330) 
IND Number 
140746 
NCT Number  
NCT03627403 
 
 
 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
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Historical Protocol Version Dates 
Version 1: 04OCT2018 
Version 2: 11SEP2019 
Version 3: 27NOV2019 
Version 4: 28APR2020 
Version 5: 17JUL2020 
Version 6: 21APR2021 
Version 7: 01MAR2022 
Version 8: 27APR2022 
Version 9: 23AUG2022 
Version 10: 16MAR2023 
 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
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TABLE OF CONTENTS 
Page 
TABLE OF CONTENTS .................................................................................................................. 3 
LIST OF ABBREVIATIONS ........................................................................................................... 5 
PROTOCOL SIGNATURE .............................................................................................................. 8 
STUDY SUMMARY........................................................................................................................ 9 
1 
OBJECTIVES ......................................................................................................................... 11 
1.1 
Primary Objective ......................................................................................................... 11 
1.2 
Secondary Objectives ................................................................................................... 11 
1.3 
Exploratory Objective(s) .............................................................................................. 11 
2 
BACKGROUND .................................................................................................................... 12 
2.1 
Myelofibrosis ................................................................................................................ 12 
2.2 
Selinexor ....................................................................................................................... 14 
2.3 
Study rationale .............................................................................................................. 15 
Selinexor Dosing ......................................................................................................................... 17 
3 
DRUG INFORMATION ........................................................................................................ 18 
3.1 
Selinexor ....................................................................................................................... 18 
4 
STUDY DESIGN.................................................................................................................... 20 
4.1 
Description.................................................................................................................... 20 
4.2 
Number of Patients ....................................................................................................... 21 
4.3 
Number of Study Centers ............................................................................................. 21 
4.4 
Study Duration .............................................................................................................. 21 
5 
ELIGIBILITY CRITERIA...................................................................................................... 22 
5.1 
Inclusion Criteria .......................................................................................................... 22 
5.2 
Exclusion Criteria ......................................................................................................... 24 
5.3 
Recruitment Strategies .................................................................................................. 25 
6 
TREATMENT PLAN ............................................................................................................. 25 
6.1 
Administration Schedule .............................................................................................. 25 
6.2 
Selinexor ....................................................................................................................... 25 
6.3 
Concomitant Medications and Therapies ..................................................................... 26 
6.4 
Duration of Therapy ..................................................................................................... 27 
7 
TOXICITIES AND DOSAGE MODIFICATION ................................................................. 29 
7.1 
Dose Modifications....................................................................................................... 29 
7.2 
Guidelines for Management of Adverse Events ........................................................... 29 
7.3 
Contraception................................................................................................................ 37 
8 
STUDY CALENDAR ............................................................................................................ 39 
9 
STUDY PROCEDURES ........................................................................................................ 43 
9.1 
Screening Evaluations .................................................................................................. 43 
9.2 
Baseline Evaluations..................................................................................................... 44 
9.3 
On Treatment Evaluations ............................................................................................ 44 
9.4 
Cycle 7 Day 1 ............................................................................................................... 45 
9.5 
Cycle 10 + (every three months) .................................................................................. 46 
9.6 
End of Treatment Evaluations ...................................................................................... 46 
9.7 
Survival Follow Up ...................................................................................................... 47 
10 CRITERIA FOR EVALUATION AND ENDPOINT ............................................................ 47 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
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10.1 
Safety ............................................................................................................................ 47 
10.2 
Efficacy ......................................................................................................................... 48 
10.3 
Stopping Rules .............................................................................................................. 48 
11 STATISTICAL CONSIDERATIONS.................................................................................... 49 
11.1 
Statistical hypothesis .................................................................................................... 49 
11.2 
Sample size determination ............................................................................................ 49 
11.3 
Statistical Analysis of Dose de-escalation .................................................................... 49 
11.4 
Population for analyses ................................................................................................. 50 
11.5 
Statistical Analyses ....................................................................................................... 50 
12 REGISTRATION GUIDELINES ........................................................................................... 51 
13 DATA SUBMISSION SCHEDULE ...................................................................................... 52 
14 CORRELATIVE STUDIES ................................................................................................... 52 
15 ETHICAL AND REGULATORY CONSIDERATIONS ...................................................... 53 
15.1 
Informed consent .......................................................................................................... 53 
15.2 
Human Subjects Protections ......................................................................................... 53 
15.3 
Institutional Review ...................................................................................................... 53 
15.4 
Data and Safety Monitoring Plan ................................................................................. 53 
15.5 
Adverse Events and Serious Adverse Events ............................................................... 54 
15.6 
SAE Reporting Requirements ...................................................................................... 56 
15.7 
Reporting of Pregnancy ................................................................................................ 58 
15.8 
Overdose ....................................................................................................................... 58 
15.9 
Abuse, Misuse, or Medication Error ............................................................................ 58 
15.10 
Occupational Exposure ................................................................................................. 59 
15.11 
Protocol Amendments .................................................................................................. 59 
15.12 
Protocol Deviations ...................................................................................................... 59 
15.13 
FDA Annual Reporting ................................................................................................ 60 
15.14 
Clinical Trials Data Bank ............................................................................................. 60 
15.15 
Record Keeping ............................................................................................................ 60 
16 APPENDICES ........................................................................................................................ 61 
16.1 
Appendix 1 - Eastern Cooperative Oncology Group Performance Status Criteria 
(ECOG) & Karnofsky Performance Scale Index (KPS) equivalency ........................................ 61 
16.2 
Appendix 2 - Ophthalmic Exam ................................................................................... 62 
16.3 
Appendix 3 - NCCN Clinical Practice Guidelines in Oncology: Antiemesis .............. 63 
16.4 
Appendix 4 - NCCN Clinical Practice Guidelines in Oncology: Anorexia/Cachexia . 65 
16.5 
Appendix 5 - International Working Group-Myeloproliferative Neoplasms Research 
and Treatment (IWG-MRT) Criteria for myelofibrosis .............................................................. 66 
16.6 
Appendix 6 - Screening Symptoms Form .................................................................... 68 
16.7 
Appendix 7 - Myeloproliferative Neoplasms Symptom Assessment Form- Total 
Symptom Score (MPN-SAF TSS) Form .................................................................................... 69 
16.8 
Appendix 8 – Primary Myelofibrosis Dynamic International Prognostic Scoring 
System (DIPSS) .......................................................................................................................... 70 
17 REFERENCES ....................................................................................................................... 71 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation or Term1 
Definition/Explanation 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
AV 
Atrioventricular 
β-HCG 
Beta-human chorionic gonadotropin 
BID 
Twice daily 
BLQ 
Below limit of quantification 
BMI 
Body mass index 
BP 
Blood pressure 
BSA 
Body Surface Area 
BUN 
Blood urea nitrogen 
Ca++ 
Calcium 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CHF 
Congestive heart failure 
CI 
Confidence interval 
Cl- 
Chloride 
CLcr 
Creatinine clearance 
Cmax 
Maximum observed concentration 
Cmin 
Trough observed concentration 
CNS 
Central nervous system 
CR 
Complete response 
CRF 
Case report form 
CT 
Computed tomography 
CTCAE 
Common Toxicity Criteria for Adverse Events 
CV 
Coefficient of variation 
CYP 
Cytochrome P450 
D/C 
Discontinue 
ECOG 
Eastern Cooperative Oncology Group 


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Abbreviation or Term1 
Definition/Explanation 
eCRF 
Electronic case report form 
DLT 
Dose Limiting Toxicity 
ECG 
Electrocardiogram 
Eg 
Exempli gratia (for example) 
ET 
Essential thrombocytosis / thrombocythemia 
FACS 
Fluorescence Activated Cell Sorting  
FDA 
Food and Drug Administration 
FDG-PET 
Fluorodeoxyglucose (FDG)-positron emission tomography (PET) 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GLP 
Good laboratory practice  
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCO3- 
Bicarbonate 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
hr 
Hour or hours 
IC50 
Half maximal inhibitory concentration 
i.e. 
Id est (that is) 
IEC 
Independent ethics committee 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional review board 
IU 
International unit 
IV 
Intravenous, intravenously 
LDH 
Lactate dehydrogenase 
LLQ 
Lower limit of quantitation 
MedRA 
Medical Dictionary for Drug Regulatory Activities 
MRI 
Magnetic resonance imaging 
MRSD 
Maximum recommended starting dose 
MTD 
Maximum tolerated dose  
NOAEL 
No-observed-adverse-effect level 


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Abbreviation or Term1 
Definition/Explanation 
NOEL 
No-observed-effect-level 
PDn 
Pharmacodynamic(s) 
PFS 
Progression Free Survival 
PK 
Pharmacokinetic(s) 
PO 
Per os (administered by mouth) 
PR 
Partial response 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QC 
Quality control 
RBC 
Red blood cell 
QD 
Once daily 
QTc 
QT interval corrected  
QTcF 
QT interval corrected using Fredericia equation 
QTcB 
QT interval corrected using Bazett’s formula 
SAE 
Serious adverse event 
SD 
Standard deviation or stable disease 
T1/2 
Terminal elimination half-life 
T3 
Triiodothyronine 
T4 
Thyroxine 
Tmax 
Time of maximum observed concentration 
TID 
Three times daily 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
ULQ 
Upper limit of quantitation 
UV 
Ultraviolet 
WBC 
White blood cell 
WOCBP 
Women of childbearing potential 
WONCBP 
Women of nonchildbearing potential 
1 All of these abbreviations may or may not be used in protocol.  
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
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PROTOCOL SIGNATURE 
I confirm that I have read this protocol, and I will conduct the study as outlined herein and according 
to the ethical principles stated in the latest version of the Declaration of Helsinki, the applicable 
ICH guidelines for good clinical practice, and the applicable laws and regulations of the federal 
government. I will promptly submit the protocol to the IRB for review and approval. Once the 
protocol has been approved by the IRB, I understand that any modifications made during the study 
must first be approved by the IRB prior to implementation except when such modification is made 
to remove an immediate hazard to the subject. 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study treatment, the conduct of the study, and the obligations of 
confidentiality. 
This document is signed electronically through submission and approval by the Principal 
Investigator at Huntsman Cancer Institute in the University of Utah IRB Electronic Research 
Integrity and Compliance Administration (ERICA) system. For this reason, the Principal 
Investigator at Huntsman Cancer Institute will not have a hand-written signature on this signature 
page.  
Instructions to multisite Principal Investigators at locations other than Huntsman Cancer Institute: 
SIGN and DATE this signature page and PRINT your name. Return the original, completed and 
signed, to the HCI Research Compliance Office. Retain a copy in the regulatory binder.  
 
 
 
____________________________________ 
_______________ 
Signature of Principal Investigator  
 
Date 
 
 
 
____________________________________ 
Principal Investigator Name (Print) 
 
 
 
____________________________________ 
Name of Institution 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
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STUDY SUMMARY 
Title 
A Phase II Study to Evaluate the Efficacy and Safety of 
Selinexor in Patients with Myelofibrosis Refractory or 
Intolerant to JAK1/2 Inhibitors 
Short Title 
Selinexor in myelofibrosis refractory or intolerant to JAK 
1/2 inhibitors 
Protocol Identifiers (IRB – internal) 
IRB # 114354 – CTO # HCI-17-HEM-13 
IND number 
140746 
Phase 
II 
Design 
Open label, non-randomized, prospective, single-arm 
study 
Study Duration 
Up to 30 months  
Study Center(s) 
Multisite 
Objectives 
To evaluate the efficacy, safety, and tolerability of 
selinexor in primary myelofibrosis (PMF), post-essential 
thrombocytosis myelofibrosis (PET-MF), or post-
polycythemia vera myelofibrosis (PPV-MF) patients 
refractory or intolerant to ruxolitinib and/or any other 
experimental JAK1/2 inhibitors 
Number of Subjects 
Up to 24 subjects 
Diagnosis and Main Eligibility Criteria 
Inclusion: 
• Diagnosis of PMF or PET-MF or PPV-MF 
• Refractory or intolerant to ruxolitinib and/or any other 
experimental JAK1/2 inhibitors 
• Age ≥ 18 years, ECOG ≤ 2 
• Life expectancy ≥ 6 months 
• Adequate hepatic, renal, and hematopoietic function 
Exclusion: 
• Prior exposure to a SINE compound, including 
selinexor  
• Radiation, chemotherapy, immunotherapy, or any 
other anticancer therapy within 2 weeks of C1D1. 
• Major surgery within 4 weeks of C1D1 
• Uncontrolled active infection requiring treatment, 
active hepatitis A, B, or C infection 
• Active gastrointestinal dysfunction affecting 
absorption or ability to swallow 
Study Product, Dose, Route, Regimen 
Selinexor, 40-80 mg orally once weekly depending on 
cohort 
Duration of administration 
Until IWG-MRT progressive disease criteria for 
leukemic transformation have been met (appendix 5),  
subject experiences an intolerable toxicity, or is no 
clinical benefit per treating physician’s discretion, 
whichever occurs first 
Reference therapy 
None 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
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Statistical Methodology 
Primary Objective: Response is defined as a 35% or 
greater reduction in spleen volume as measured by MRI 
or CT abdomen from baseline to after 6 cycles of 
treatment. A sample size of 18 evaluable subjects will 
provide 83% power at one-sided alpha = 0.05 to reject a 
response rate of 15% (the null hypothesis) using a one 
sample exact test for a binomial proportion provided the 
true response rate is 42%. The null hypothesis will be 
rejected if 6 or more out of 18 subjects respond. The 
planned sample size is 24 to allow for up to a 25% 
dropout rate.  Change and percentage change in 
radiographic spleen volume as well as radiographic 
spleen response rates will be summarized using 
descriptive statistics. The mean, range, standard deviation 
and 95% confidence interval will be reported for change 
and percent change in spleen volume.  
 
Secondary Objectives: adverse events will be evaluated 
and graded as per the CTAEv5.0 and safety endpoints 
will be analyzed by descriptive statistics. Additional 
efficacy endpoints will be analyzed descriptively: 
response rates (overall response and symptoms response 
by IWG-MRT criteria) will be determined by tabulating 
the number and proportion of subjects that respond. The 
mean, standard deviation, minimum, and maximum time 
to response will be computed for the subset of patients 
that have a response. 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
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1 
OBJECTIVES 
1.1 
Primary Objective 
To assess the efficacy of selinexor on spleen volume reduction in subjects with 
myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or 
any other experimental JAK1/2 inhibitors. 
 
Primary Endpoint:  
Response rate defined as the proportion of subjects with ≥ 35% reduction in spleen 
volume as measured by MRI or CT abdomen from baseline to after six cycles of 
treatment. Patients who do not complete six cycles of therapy will be considered non- 
responders, but their data will still be reported. Patients who do not complete six cycles of 
treatment will receive an MRI at cycle 7 day 1, or at discontinuation of therapy (see 
section 11.4.2). 
1.2 
Secondary Objectives 
 
To assess the safety/tolerability and further characterize the safety profile of selinexor 
in PMF, PET-MF, or PPV-MF patients refractory or intolerant to ruxolitinib and/or any 
other experimental JAK1/2 inhibitors. 
Secondary Endpoints: rate of adverse events (AEs) and serious adverse events (SAEs). 
 
To further assess the efficacy and clinical activity of selinexor (by means of reduction 
in symptoms, overall response, and overall survival) in subjects with myelofibrosis 
(PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other 
experimental JAK1/2 inhibitors. 
Secondary Endpoints:  
• Percent change of spleen volume as measured by MRI or CT abdomen. 
• Proportion of patients with ≥ 50% reduction of total symptoms score as 
measured by the MPN-Symptoms Assessment Form (MPN-SAF) from 
baseline to after 6 cycles of treatment. Patients who do not complete six cycles 
of therapy will be considered non responders, but their data will still be 
reported. Patients who do not complete six cycles of treatment will receive the 
MPN-SAF assessment at cycle 7 day 1, or at discontinuation of therapy (see 
section 11.4.2). 
• Overall response rate according to the 2013 IWG-MRT consensus criteria for 
treatment response in primary and secondary MF (post-PV and post-ET).  
• Overall survival at 24 months from the initiation of study therapy  
1.3 
Exploratory Objective(s) 
 
To assess the effects of selinexor on MF bone marrow fibrosis grade. 
Exploratory Endpoints: changes in bone marrow fibrosis grade and cytogenetic 
abnormalities from baseline.  


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To assess the effects of selinexor on duration of spleen volume reduction.  
Exploratory Endpoints: Duration of ≥ 35% reduction in spleen volume as measured by 
MRI or CT abdomen. 
 
To assess the effects of selinexor on levels of circulating inflammatory cytokines. 
Exploratory Endpoints: change in circulating inflammatory cytokine profile including 
but not limited to IL-6, IL-1β, tumor necrosis factor (TNF), TNFRII. 
 
To assess the effects of selinexor on JAK2 or CALR or MPL mutant allele burden. 
Exploratory Endpoints: change in allele burden of JAK2V617F, MPLW515 and S505 
and CALR exon 9.   
 
To assess the effects of selinexor on genetic mutations by NGS. 
Exploratory Endpoints: changes in genetic mutations by NGS from baseline.  
 
To assess the effects of selinexor on other pharmacodynamic markers. 
Exploratory Endpoints: change in other pharmacodynamic markers levels from C2D1 
pre dose to 4 hours post dose. 
 
To explore whether a customized tool can be developed to estimate spleen volume 
based on MRI or CT abdomen. 
Exploratory Endpoints: correlation between spleen volumes calculated using the 
standard institutional method and a new experimental method. 
 
To find predictive marker of selinexor response, from DNA and RNA sequencing. 
Exploratory Endpoints: to identify predictive markers of selinexor response from DNA 
and RNA sequencing.  
2 
BACKGROUND 
2.1 
Myelofibrosis 
The classic BCR-ABL negative myeloproliferative neoplasms (MPNs) encompass 
polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). 
MF is characterized by clonal hematopoietic stem cell proliferation and bone marrow reticulin 
fibrosis, leading to ineffective erythropoiesis, elevated inflammatory cytokines, and marked 
extramedullary hematopoiesis.1 The prevalence of MF in the United States is estimated to be 
4-6 cases per 100,000 people with a median age of 60 to 65 years at diagnosis.2 MF can 
present de novo (primary MF) or as secondary from PV (post-PV MF or PPV-MF) or ET 
(post-ET MF or PET-MF). Cytopenias, thromboembolism, symptomatic splenomegaly, and 
leukemic transformation account for the major morbidity of MF patients. The survival of MF 
patients is significantly reduced compared to age-matched controls as well as PV and ET 
patients. In addition, many MF patients have low quality of life (QoL) and experience 
debilitating constitutional symptoms including fatigue, anorexia, night sweats and weight 
loss.3,4 Various tools have been developed and validated in large cohorts of MPN patients for 


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the assessment of disease-related symptoms. The MPN symptom assessment form (MPN-
SAF) is a 27-item tool that allows for objective assessment of MPN symptoms and is 
validated in large cohort of MPN patients (including MF). A short abbreviated tool, the MPN-
SAF Total Symptom Score (MPN-SAF TSS), includes the 10 most common symptoms in 
patients with MPN and is also a validated tool to assess symptom burden in MF patients.5,6 A 
≥ 50% reduction in the total symptoms score is considered to be a valid end point in clinical 
trials of MF patients.7- 10  
A number of prognostic scoring systems have been developed for MF and are currently used 
in the clinic to estimate overall survival, risk of leukemic transformation, and also guide 
treatment decisions. The International Prognostic Scoring System (IPSS) was developed based 
on certain clinical features at diagnosis including age > 65 years, presence of constitutional 
symptoms, hemoglobin < 10 g/dL, white blood cell count > 25,000/µL and peripheral blood 
blasts > 1%.11 IPSS stratifies patients to low, intermediate-1, intermediate-2, and high risk 
based on the presence of 0, 1, 2 or ≥ 3 of the variables. The Dynamic International Prognostic 
scoring system (DIPSS) is a time-dependent risk model which takes into account the 
development of anemia over time in addition to the IPSS variables (as shown in Table 1).12,13  
Constitutive activation of JAK/STAT signaling through mutations in JAK2 (JAK2V617F, 50% 
to 60%), calreticulin (CALR, 20-30%), or MPL (W515L and others, 5-7%) is characteristic of 
MF.14 Several co-existing mutations are reported, most commonly involving genes associated 
with epigenetic regulation such as EZH2, ASXL1, TET2 and DNMT3A. ASXL1 mutations are 
shown to be independently associated with inferior overall survival, and in one study, CALR 
mutations were found to be associated with a more indolent phenotype.15 So far, none of the 
molecular abnormalities outside of those involving JAK/STAT activation (JAK2, MPL and 
CALR) have led to therapeutic advances.  
Table 1: Risk stratification of myelofibrosis by Dynamic International Prognostic 
Scoring System (DIPSS) 
Total risk score 
Risk category 
Median overall survival  
0 
Low 
not reached 
1 to 2 
Intermediate-1 
14.2 years 
3 to 4  
Intermediate-2 
4 years 
5 to 6  
High 
1.5 years 
Until 2012, MF treatment was limited to chemotherapy to control myeloproliferation 
(hydroxyurea, busulfan), supportive care measures such as cytokines to improve cytopenias 
(erythropoietin, G-CSF), and prednisone or immunomodulatory drugs (thalidomide and 
lenalidomide).16 The discovery of JAK2V617F mutations in MF patients led to the development 
of ruxolitinib (RUX), a JAK1/2 inhibitor, which was approved in 2012 for high-risk and 
intermediate-2 risk MF patients. Two large randomized Phase 3 studies conducted in the 
United States and Europe showed superiority of RUX over placebo or best available therapy 
(BAT) in major endpoint (spleen volume reduction) and improvement in constitutional 
symptoms and QoL.17,18 In a more recent update, a trend toward improved overall survival 
was reported. However, some patients demonstrate inadequate response to RUX or develop 
progressive increase in spleen size after an initial response (refractory disease). Additionally, 
thrombocytopenia frequently limits dose intensity and renders many patients ineligible for 


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RUX. More importantly, the effect of RUX treatment on the natural history of MF is minimal. 
Except in few rare patients, RUX does not significantly affect the JAK2V617F mutant allele 
burden.19 Pacritinib, a JAK2-specific inhibitor with less myelosuppressive effects than RUX, 
has been found to be superior to best available therapy (BAT) but has not yet been approved 
due to increased bleeding and cardiovascular events.7,9 Momelotinib, another JAK1/2 
inhibitor, showed responses in term of spleen volume reduction and anemia response, but 
failed to show superiority over BAT in patients previously treated with ruxolitinib.8,10 Further 
studies are currently ongoing to evaluate the clinical benefits of momelotinib in comparison to 
danazol in symptomatic and anemic MF patients (NCT04173494). Fedratinib, a JAK2-
selective inhibitor is recently approved for intermediate-2 or high risk MF patients based on 
JAKARTA study, which showed superiority of fedratinib over placebo in major end points 
(spleen volume reduction and symptoms). However similar to RUX, no meaningful changes 
were observed in JAK2 mutant allele burden indicating minimal effect of fedratinib on the 
disease clone (Pardanani JAMA oncology 2015). Anemia and thrombocytopenia were 
common with fedratinib. More importantly, serious and fatal encephalopathy has occurred in 
some patients leading to a Boxed warning and treating physicians are advised to assess 
thiamine levels prior to starting fedratinib and periodically during treatment. Allogeneic stem 
cell transplant is the only available therapy for patients who are refractory or intolerant to 
RUX but is limited by significant transplant-related morbidity and mortality and many MF 
patients are ineligible.20 Although some studies reported high success rates with allogeneic 
stem cell transplantation in MF, subsequent studies failed to replicate similar level of success. 
Therefore, novel therapeutic approaches are needed to improve outcomes. 
2.2 
Selinexor 
Selinexor (also known as KPT-330) is a small molecule, oral, first-in-class, potent, slowly 
reversible, covalent-binding Selective Inhibitor of Nuclear Export (SINE) that specifically 
blocks the karyopherin protein exportin 1 (XPO1), also called chromosome region 
maintenance 1 (CRM1). XPO1 is overexpressed 2-4 fold in all cancers studied to date and 
overexpression is frequently correlated with poor prognosis and/or reduced survival, 
suggesting that XPO1 could have a direct role in the etiology of the malignant phenotype. 
XPO1 is the exclusive nuclear transporter for shuttling the major tumor suppressor proteins 
(TSPs) and other growth regulators out of the nucleus. Since TSPs require nuclear localization 
to mediate their deoxyribonucleic acid (DNA) damage assessment/tumor suppressing 
functions, nuclear export leads to their functional inactivation and/or proteasome-dependent 
cytoplasmic degradation. In addition, XPO1 mediates the nuclear-to-cytoplasmic transport of 
the mRNAs for several oncoproteins (associated with the carrier molecule eIF4E) including c-
Myc, Cyclin D, BTK, Flt3 and Bcl2 family proteins leading to increased cytoplasmic 
ribosomal translation and higher levels of these pro-survival proteins. Blockade of XPO1 
leads to marked accumulation of TSPs in the nucleus of all cells, leading to cell cycle arrest at 
the G1±G2 checkpoints, inhibition of DNA damage repair (DDR), inhibition of the NF-κB 
pathway, and modulation of the immune checkpoint response. Cells with damaged genomes 
(i.e., cancer cells) undergo apoptosis, whereas undamaged normal cells remain in cell cycle 
arrest until the XPO1 block is released. Blockade of XPO1 similarly leads to decrease in the 
nuclear-to-cytoplasmic transport of mRNAs for several oncoproteins with consequent 
reductions in their protein levels.  


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2.3 
Study rationale 
 
Nuclear-cytoplasmic transport and oncogenesis 
Chromosomal maintenance 1 (CRM1), also known as exportin-1 (XPO-1), promotes the 
energy-dependent directional transport of cargo proteins with a leucine-rich nuclear export 
signal (NES) through the nuclear pore complex (NPC) into the cytoplasm. NES-containing 
cargo proteins in the nucleus form a trimeric complex with CRM1 and the GTP-bound form 
of the small GTPase Ran. This complex is shuttled through the NPC into the cytoplasm, 
where the GTP bound to Ran is hydrolyzed to GDP (facilitated by RanGTPase activating 
protein, RanGAP), which in turn lowers the affinity for cargo, causing its release. CRM1 is 
then shuttled back into the nucleus, where the transport cycle resumes. The RanGTP/RanGDP 
gradient provides the energy for the directional cargo transport. CRM1 cargos include a 
number of cancer-relevant proteins such as p53, p21, p27, PP2A and surviving.21 Some cancer 
cells rely on effective NCT to inactivate nuclear tumor suppressors (e.g., p53) or to activate 
cytoplasmic oncogenes (e.g., survivin). For example, it has been shown that CML cells with 
BCR-ABL1 – independent imatinib resistance are sensitive to inhibition of NCT by 
knockdown of Ran.22 The potential of inhibiting CRM1 for cancer therapy has been 
recognized for some time. A series of compounds (selective inhibitors of nuclear export, 
SINE) are recently developed that inhibit XPO-1 mediated NCT. The most advanced 
compound, selinexor (KPT-330), is active in pre-clinical cancer models; early clinical trials at 
several cancer indications are ongoing.  
 
Nuclear-cytoplasmic transport and myelofibrosis 
Aberrant JAK/STAT pathway activation is central to the pathogenesis of myelofibrosis. 
However, JAK inhibitors, such as ruxolitinib, only reduce symptoms, but are not curative. To 
identify novel targets in myelofibrosis, irrespective of somatic mutation status, a short hairpin 
RNA library screen was performed on JAK2V617F mutated HEL cells. HEL cells were 
subjected to a lentiviral shRNA library (Human Module 1, Cellecta, Inc.) containing 27,239 
noncontrol shRNAs targeting 5,034 genes involved in cell signaling, with 5-6 shRNAs per 
gene as described before.22 Candidate genes were selected on the basis of 10-fold depletion ≥ 
3 shRNAs and reduction in ≥ 3 shRNAs targeting the same gene. (See Table 2). Nuclear-
cytoplasmic transport (NCT) proteins, RAN and RANBP2 were amongst the top 20 candidate 
genes, suggesting that HEL cells may be highly dependent on NCT.23  
Table 2: Top 20 candidate genes from the shRNA library screen in HEL cells 
Rank 
Gene Symbol 
Median Fold 
Depletion 
Gene Name 
1 
PSMB2 
59 
proteasome subunit beta 2 
2 
RAN 
50 
RAN family GTPase, Ras 
superfamily GTPase 
3 
SHFM1 
45 
26S proteasome complex 
subunit 
4 
IL28B 
43 
interferon lambda 3 
5 
PSMD13 
41 
proteasome 26S subunit, non-
ATPase 13 
6 
POLR2F 
40 
RNA polymerase II subunit F 
7 
RPL11 
40 
ribosomal protein L11 


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8 
PSMD2 
38 
proteasome 26S subunit, non-
ATPase 2 
9 
SSRP1 
36 
structure specific recognition 
protein 1 
10 
RPL12 
36 
ribosomal protein L12 
11 
HMGCR 
35 
3-hydroxy-3-methylglutaryl-CoA 
reductase 
12 
RPL6 
34 
ribosomal protein L6 
13 
HNRNPC 
34 
heterogeneous nuclear 
ribonucleoprotein C (C1/C2) 
14 
ITK 
33 
IL2 inducible T-cell kinase 
15 
SIN3A 
33 
SIN3 transcription regulator 
family member A 
16 
RANBP2 
33 
RAN binding protein 2 
17 
PSMA3 
33 
proteasome subunit alpha 3 
18 
PSMB7 
33 
proteasome subunit beta 7 
19 
LOC402057 
32 
unknown gene, 
NM_001080499.1 
20 
PSMB3 
32 
proteasome subunit beta 3 
To validate the screen results, HEL and another JAK2V617F mutant SET-2 cells were stably 
transduced with doxycycline (DOX)-inducible shRAN. DOX-induced knockdown of RAN, 
reduced cell viability, strongly increased apoptosis and reduced colony formation (data not 
shown). Inhibition of XPO-1 by selinexor was found to phenocopy the results of RAN 
knockdown in HEL and SET-2 cells (Figure 1 A and B). Selinexor selectively decreased 
proliferation of primary MF CD34+ cells (Fig. 1C), decreased colony formation ability (Figure 
1D), and increased apoptosis (Figure 1E and F). To evaluate the role of NCT in vivo, selinexor 
was tested in a mouse model of JAK2V617F driven myeloproliferative neoplasm. BALB/c mice 
were infected with pMIG-JAK2V617F containing retrovirus after lethal total body irradiation. 
Animals develop advanced MPN characterized by severe myeloid expansion, bone marrow 
reticulin fibrosis and splenomegaly in 3-4 weeks. Animals were treated with vehicle, selinexor 
alone or in combination with RUX. Selinexor decreased white blood cell counts and granulocytes 
and MPN clone as measured by GFP positive fraction in peripheral blood, spleen and bone 
marrow both as single agent and in combination with RUX (animal data not shown). These data 
provide a strong rationale for targeting NCT in MF. 23 


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Figure 1: Preclinical data. 
 
Analysis of the efficacy of KPT-330 against JAK2V617F-positive human cell lines shows that KPT-330 is 
comparable to ruxolitinib (A, B). KPT-330 prevents the growth of primary myelofibrosis cells (red bars) at 50 
and 100 nM, while these doses are less effective against cord blood cells (black bars; C). KPT-330 is effective at 
reducing colony formation by MF cells and shows minimal effect against cord blood cells (D). Analysis of 
apoptosis by Annexin V and 7-AAD labeling revealed selectivity for myelofibrosis cells over cord blood cells 
(E, F). * denotes p value below 0.05. 
 
Dose Schedule Rationale 
Selinexor Dosing 
Selinexor is approved for the treatment of adult patients with relapsed or refractory multiple 
myeloma who have received at least 4 prior therapies and whose disease is refractory to at 
least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 
monoclonal antibody. 
In addition, selinexor is currently under investigation in ongoing Phase 1-3 trials in patients 
with various hematologic malignancies. In the phase 1 study dosing has safely reached 60 
mg/m2 (~100 mg) twice weekly (cleared DLT; total weekly dose 120 mg/m2 [~200 mg]). The 
MTD has not been reached in this study, but two DLTs were observed at a dose of 85 mg/m2 
in a parallel ongoing study (KCP-330-002) of selinexor in patients with advanced solid 
tumors. Based on these findings, the MTD for selinexor in patients with B-cell malignancies 


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is 60 mg/m2 twice weekly (120 mg per week or 480 mg per cycle). Among heavily pretreated 
patients enrolled in this ongoing Phase 1 trial, selinexor-related Grade 3-4 thrombocytopenia 
has been observed primarily at total weekly doses of ≥ 46 mg/m2 and Grade 3-4 neutropenia at 
total weekly doses ≥ 60 mg/m2. Overall, increased rates of infection associated with selinexor 
have not been reported, however greater incidences of sepsis were seen with selinexor vs. PC 
in elderly patients with RR AML receiving doses > 60 mg of selinexor in study KCP-330-008. 
Going forward, selinexor will be administered primarily as fixed milligram doses, as analyses 
of Phase 1 PK data indicated that exposure is not strongly correlated with BSA. Based on 
tolerability, safety, efficacy, and DLT evaluations, the following doses are recommended  as a 
single agent for current and future Phase 2 and 3 studies: 60 mg BIW in elderly AML, 60 mg 
BIW in NHL, and 80 mg BIW in multiple myeloma (in combination with dexamethasone 20 
mg BIW). Selinexor in combination however is administered on a weekly schedule and at 
doses of 60-100 mg.   
To date, 12 patients with myelofibrosis were dosed with selinexor in this study. The starting 
dose of selinexor was 80 mg weekly in the first six patients.  After 3 out 6 patients required 
dose reduction due to grade 2 weight loss. The starting dose of selinexor was decreased to 60 
mg weekly for subsequent patients. Additional six patients were enrolled at starting dose of 60 
mg weekly. Of all the 12 patients, 7 required dose reduction to 40 mg weekly. Grade 2 weight 
loss occurred in 5 of 7 patients that required dose reduction to 40 mg weekly.  At this time, 4 
patients remain on selinexor treatment, 2 on 60 mg weekly dose and 2 on 40 weekly dose. The 
starting dose of selinexor will be decreased to 40 mg weekly for the remaining 12 expected 
patients.  
3 
DRUG INFORMATION 
3.1 
Selinexor 
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor specifically 
blocks nuclear export by binding to the nuclear export protein XPO1. 
Refer to the most recent IB for detailed background information on selinexor. The following 
information is taken from the IB 
 
Pharmacology 
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and 
inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor 
proteins (TSPs). Transient retention of TSPs in the nucleus at high levels via XPO1 blockade 
activates their cell cycle checkpoint and genome surveying actions. This leads to the death of 
nearly all types of malignant cells, whereas normal cells undergo transient cell cycle arrest 
and recovery when the export block is released. The reactivation of multiple tumor suppressor 
pathways and inhibition of translation of key pro-survival proteins through inhibition of a 
non-redundant, single protein represents a novel approach to the treatment of neoplastic 
diseases including those with multiple genomic alterations and resistance mechanisms.  
Selinexor has shown broad activity in a variety of in vitro and animal cancer studies.  


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Physical and Chemical Properties 
Selinexor, also known as KPT-330, has a molecular weight of 443.31 g/mol and a molecular 
formula of C17H11F6N7O. Its chemical name is (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-
1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide. 
 
Pharmaceutical Properties and Formulation  
20 mg tablets for oral administration will be supplied in blister packs of 12. 
Selinexor 20 mg tablets are manufactured via roller compaction dry granulation (RCDG) and 
contain 1.25% by weight of the API as well as microcrystalline cellulose ([Avicel PH101], 
binder/filler); croscarmellose sodium ([Ac-Si-Sol], disintegrant); Kollidon 30 powder 
([polyvinylpyrrolidone povidone], solubilizing agent); colloidal silicon dioxide ([M5-P], anti-
caking agent); magnesium stearate (lubricant). Additional inactive excipients include 
microcrystalline cellulose [Avicel 102], croscarmellose sodium, colloidal silicon dioxide, 
sodium lauryl sulphate, and magnesium stearate are blended with the granulated material, and 
compressed to make tablets. The compressed tablet cores are coated with Opadry II clear 
(undercoat) and blue (topcoat) to provide product formulation. 
 
Clinical Safety 
To date, more than 3226 patients with hematologic or solid tumors have received selinexor in 
clinical studies (including Karyopharm-sponsored studies and Investigator-sponsored studies) 
in > 10 disease indications. The majority of patients were treated with selinexor as a single 
agent but > 300 patients received selinexor in combination with a diverse array of other 
anticancer agents. Single-agent Phase 1 studies with oral selinexor have been conducted in 
advanced hematological malignancies including MM, acute myeloid leukemia (AML), NHL, 
and chronic lymphocytic leukemia; in solid tumors; and in soft tissue and bone sarcomas. 
Broad antitumor activity has been observed in all of these studies. In addition, Phase 2 studies 
are ongoing in MM, AML, diffuse large B-cell lymphoma, Richter’s transformation, 
glioblastoma, gynecological malignancies, and dedifferentiated liposarcoma (Phase 2 and 3). 
Additional information about clinical studies of selinexor is available in the selinexor IB. 
Pharmacokinetics 
Oral selinexor pharmacokinetics (PK) are predictable, approximately dose-proportional, and 
exhibit moderate- to moderately-high inter-patient variability across a wide range of doses in 
male and female patients with advanced hematological malignancies or solid tumors. 
Additional details are available in the selinexor IB. 
Safety and Efficacy  
To date, 3226 patients with hematologic or solid tumors had received at least one dose of 
selinexor in Company Sponsored (CSTs), Investigator Sponsored (ISTs) or Compassionate 
Use Trials and are included in the preliminary safety analyses provided in the UB in this IB. 
These 3226 patients include 2076 patients from CSTs, 1016 patients from ISTs, and 130 
patients from compassionate use trials. Safety data from all CSTs, ISTs and compassionate 
use trials are reviewed at least quarterly by Karyopharm at Safety Review Committee 
meetings. 


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In ongoing clinical studies, the most common AEs reported as at least possibly related to 
selinexor (incidences in parentheses) have been low-grade nausea (65.1%), fatigue (57.9%), 
anorexia (51%), thrombocytopenia (52.1%), vomiting (38.2%), and diarrhea (36%). Most of 
these AEs can be managed effectively with dose modification and/or supportive care initiated 
prior to first dose.  
Since clinical trials began with selinexor, 3 acute cerebellar syndrome (ACS) cases have been 
reported in 1 adult (pancreatic cancer, index case) and 2 pediatric (refractory AML) patients in 
the selinexor development program to date (including CSTs and ISTs). Symptoms of ACS can 
include a sudden loss of coordination, balance, difficulty walking or abnormal speech. All of 
these cases occurred in dose escalation studies at high doses of selinexor (85 mg/m2 in the 
adult and 70 mg/m2 in the children and were reversible. The maximum doses in adults (70 
mg/m2) and children (55 mg/m2) have been established based largely on these events. 
Reproductive Risks 
Macroscopic and microscopic changes in reproductive organs were noted during rat and 
monkey toxicology studies, most of which partially or fully resolved during the recovery 
period. The long-term effects of these changes on reproductive potential are unknown. 
Secondary developmental effects due to reduced maternal body weights were also noted 
during a study on rat embryo/fetal development. 
It is unknown whether similar effects may occur or whether selinexor might have reproductive 
toxicity in humans and as such, patients must agree to use effective contraception (refer to 
Section 7.3 for details) during the study and for 3 months following the last dose of study 
treatment. 
Nursing Mothers 
It is not known whether selinexor is excreted in human milk. Because many drugs are 
excreted in human milk, and the effect of selinexor on newborns is unknown, selinexor should 
not be administered to women who are nursing. 
Pediatric Use 
ISTs of selinexor in pediatric patients with leukemia and solid tumors are ongoing as of 31 
March 2017, and additional studies in pediatric patients with other malignancies are planned. 
Geriatric Use 
Many of the patients who participated in selinexor clinical studies have been > 65 years old, 
however no formal studies on the use of selinexor in geriatric patients have been performed.  
4 
STUDY DESIGN 
4.1 
Description 
This is a phase II, open label, prospective, single-arm study evaluating the efficacy and safety 
of selinexor in patients with PMF or secondary MF (PPV-MF or PET-MF) who are refractory 
or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. As of protocol 
version 7, Selinexor will be administered orally at a starting dose of 40 mg once weekly due 
to previous toxicity rates. Prior to protocol version 7, 6 patients were treated with a starting 


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dose of 80 mg once weekly and an additional 6 patients were treated with a starting dose of  
60 mg once weekly. 
 
4.2 
Number of Patients 
The study will enroll up to 24 patients. The power calculation for efficacy is based on a 
sample size of 18 response-evaluable patients. The sample size was set to 24 to allow for 
enrollment of up to 6 patients who are not evaluable.  
4.3 
Number of Study Centers 
This is a single-center study to be conducted at Huntsman Cancer Institute at the University of 
Utah, Salt Lake City, Utah.  
4.4 
Study Duration  
The estimated duration of enrollment will be 30 months. The primary objective will be 
evaluated after 6 cycles of selinexor (cycle 7 day 1) treatment. Selinexor treatment will 
continue thereafter as long as the study drug is tolerated and subject does not meet 
discontinuation criteria. After discontinuation of the study drug, patients will be followed for 
survival. It is estimated that each patient will participate in the study for approximately 24 
months. Therefore, the estimated study duration is about 60 months.  
 
 


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5 
ELIGIBILITY CRITERIA 
This eligibility checklist is used to determine patient eligibility and filed with enrolling 
investigator’s signature in the patient research chart.  
Patient No. ______________________ 
Patient’s Initials: (L,F,M) _________________ 
5.1 
Inclusion Criteria 
Yes/No (Response of “no” = patient ineligible) 
 
_____ Male or female subject aged ≥ 18 years. 
 
_____ Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
 
_____ Diagnosis of primary myelofibrosis (PMF), post-essential thrombocytosis 
myelofibrosis (also known as thrombocythemia) (PET-MF) or post-polycythemia vera 
myelofibrosis (PPV-MF).  
 
_____ Life expectancy ≥ 6 months. 
 
_____ Prior treatment with ruxolitinib or any experimental JAK1/2 inhibitor with any 
one or more of the following: 
a. Inadequate response after being on ≥ 3 months of treatment defined by:  
i. 
Palpable spleen ≥ 10 cm below the left subcostal margin on physical 
examination at the screening visit OR 
ii. 
Palpable spleen ≥ 5cm below the left subcostal margin on physical 
examination at the screening visit AND active symptoms of MF at the 
screening visit defined presence of 1 symptom score of ≥ 5 or two symptom 
scores each of ≥ 3 using the Screening Symptoms Form (Appendix 6)  
b. Intolerant to ruxolitinib and/or other JAK1/2 inhibitors due to any grade ≥ 3 
non-hematologic AEs of or any grade ≥ 2 AEs requiring treatment 
discontinuation AND palpable spleen ≥ 5cm below the left subcostal margin on 
physical examination at the screening visit.  
 
_____ Adequate organ function as defined as:  
• Hematologic (≤ 28 days prior to C1D1): 
o Total white blood cell (WBC) count ≥ 1000/mm3 
o Absolute neutrophil count (ANC) ≥ 500/mm3 
o Hemoglobin ≥ 7 g/dL 
o Platelet count ≥ 30,000/mm3  
For patients receiving transfusion and growth factor support, the following 
delays must be observed between the last administration and hematologic 
laboratory screening assessments: 


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• For hematopoietic growth factor support (including erythropoietin, 
darbepoetin, granulocyte-colony stimulating factor [G-CSF], 
granulocyte macrophage-colony stimulating factor [GM-CSF], and 
platelet stimulators [e.g., eltrombopag, romiplostim, or interleukin-11]): 
at least 2 weeks. 
Growth factor support, RBC and/or platelet transfusions are allowed as 
clinically indicated per institutional guidelines during the study. 
• Hepatic (≤ 28 days prior to C1D1): 
o Total bilirubin < 1.5 × ULN except in patients with indirect 
hyperbilirubinemia due to hemolysis or gilbert’s syndrome where total 
bilirubin should be <5X ULN  
o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
< 2.5 × ULN. 
• Renal (≤ 28 days prior to C1D1): 
o Estimated creatinine clearance (CrCl) ≥ 20 mL/min using the Cockcroft 
and Gault formula [(140-Age) × Mass (kg)/(72 × creatinine mg/dL), 
multiply by 0.85 if the patient is female] OR 
 
_____ Female patients of childbearing potential must have a negative serum pregnancy 
test (≤ 3 days prior to C1D1).  
 
_____ Female patients of childbearing potential must agree to use 2 methods of 
contraception throughout the study and for 3 months following the last dose of study 
treatment (including 1 highly effective and 1 effective method of contraception as 
defined in section 7.4)  
 
_____ Male patients must use an effective barrier method of contraception if sexually 
active with a female of childbearing potential. 
 
_____ Recovery to baseline or ≤ Grade 1 CTCAE v. 5.0 from toxicities related to any 
prior treatments including ruxolitinib or other experimental agents unless AE(s) are 
clinically nonsignificant and/or stable on supportive therapy. 
 
_____ Able to provide informed consent and willing to sign an approved consent form 
that conforms to federal and institutional guidelines.  


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5.2 
Exclusion Criteria 
Yes/No (Response of “yes” = patient ineligible) 
 
_____ Prior exposure to a SINE compound, including selinexor. 
 
_____ Patients who are below their ideal body weight and would be unduly impacted 
by changes in their weight, in the opinion of the investigator, will be excluded. 
 
_____ Uncontrolled active infection requiring parenteral antibiotics, antivirals, or 
antifungals ≤ 1 week prior to C1D1. Patients on prophylactic antibiotics or with a 
controlled infection ≤ 1 week prior to C1D1 are eligible. 
 
_____ Radiation, chemotherapy, immunotherapy, or any other anticancer therapy 
(including investigational therapies) ≤ 2 weeks  
 
_____Ruxolitinib or other JAK1/2 inhibitors ≤ at least 3 days or 5 half-lives prior to 
C1D1.  
 
_____ Major surgery ≤ 4 weeks prior to C1D1. 
 
_____ Known active hepatitis A, B, or C infection; or known to be positive for 
hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen. 
 
_____ Any active gastrointestinal dysfunction interfering with the patient’s ability to 
swallow tablets, or any active gastrointestinal dysfunction that could interfere with 
absorption of study treatment. 
 
_____ Any life-threatening illness, organ system dysfunction, or serious psychiatric, 
medical, or other conditions/situations which, in the investigator's opinion, could 
compromise a patient’s ability to give informed consent, safety, or compliance with the 
protocol. 
 
_____ Contraindication to any of the required concomitant drugs or supportive 
treatments. 
 
______ Subjects taking prohibited medications as described in Section 6.3. Following 
discontinuation of prohibited medications, a washout period is required prior to 
initiating study treatment (the duration of the washout must be as clinically indicated, 
e.g., at least five half-lives). 
 
______ Subjects who are breastfeeding and unwilling to stop while on study. 
I certify that this patient meets all inclusion and exclusion criteria for enrollment onto this 
study.  
_______________________________________ 
 
______________ 
____________ 
Investigator Signature  
 
 
 
 
Date  
 
Time 
 
 


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5.3 
Recruitment Strategies 
Potential patients will be identified by Investigators in the setting of their outpatient clinics. 
6 
TREATMENT PLAN 
6.1 
Administration Schedule 
The schedule is based on 28-day cycles. 
For patients enrolled after protocol version 7, Selinexor will be administered by oral route, 
beginning at 40 mg once weekly. Prior to protocol version 7, the starting dose of selinexor 
was 60 mg and 80 mg once weekly.  
In case of toxicity at the starting dose level, dose modifications will be implemented as 
described in Section 7.1.  Treating investigators may consider increasing the dose to 60 mg 
once weekly after 12 weeks of treatment in the absence of grade 2 or higher weight loss. The 
dose increase must be done after documented consultation with PI and medical monitor. 
6.2 
Selinexor 
 
How Supplied, Stored, Packaged and Labeled 
Selinexor will be provided by Karyopharm Therapeutics Inc. as coated, immediate-release 
oral tablets in strengths of 20 mg in wallet-sized blister packs which will be maintained by site 
Investigational pharmacy.  
Selinexor 20 mg tablets are to be stored in a locked and secured area with access restricted to 
the site staff at room temperature (below 30 °C) in clear blister strips that are composed of 
either polyvinyl chloride (PVC)/polyethylene (PE)/polychlorotrifluoroethylene (PCTFE) clear 
film blister with a foil paper backing or (PVC)/(PCTFE)/(PVC) clear film blister with a foil 
paper backing. Room temperature storage is recommended, refrigerated is acceptable. Tablets 
should not be stored frozen. 
The blistered packaged product will be placed in paperboard secondary packaging, to which 
labeling materials will be affixed. 
All labels will include conditions for storage, lot number, and other information required by 
the Food and Drug Administration (FDA), International Council for Harmonisation (ICH), 
and/or Annex 13, as well as all local regulations for investigational medication. 
Selinexor tablets are currently in on-going stability studies. The expiry will be based on 
concurrent stability studies and extended during the course of the study as further stability 
data becomes available. 
 
Preparation and Administration 
Qualified personnel, familiar with procedures that minimize undue exposure to themselves 
and the environment, should undertake the handling and safe disposal of selinexor in a self-
contained and protective environment No special preparation is required.  
Selinexor should be taken with at least 120 mL (4 ounces) of fluids (water, juice, etc.) at 
approximately the same time each dosing day.  


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Selinexor tablets should be swallowed whole (not crushed) to prevent an increased risk of 
dermatologic toxicity if the powder comes in contact with skin. For doses of oral medications 
to be taken on non-clinic days, patients will be provided with medication to take home. 
Missed Doses 
If a dose was missed, the dose can be made up and the schedule should be altered to maintain 
at least 36 hours between two consecutive doses. 
If a dose must be skipped (e.g., due to recommendation of treating physician), the next dose 
will be taken as per schedule. Doses should not be administered less than 36 hours apart and 
all missed and delayed doses should be documented. 
Vomited Doses 
If a dose is vomited within 1 hour of ingestion, it will be replaced. If vomiting occurs more 
than 1 hour after dosing, it will be considered a complete dose. 
 
Accountability and Compliance 
Selinexor must be requested by submitting an order form directly to the drug depot and will 
be shipped directly to site’s Investigational Drug Services.  
The investigator, or a responsible party designated by the investigator, must maintain an 
adequate record of receipt, distribution, and return of all study drugs in the form of a Drug 
Accountability Form. Such records must be provided to the drug supplier upon request.  
Subjects are required to bring all used packs and any unused investigational product (IP) when 
they visit to the site at the end of each cycle. Compliance will be assessed by discussion with 
the patient and confirmed by pill count. Any deviations and missed doses (including reasons 
for the deviation or missed doses) will be recorded in the site’s internal database and drug 
accountability logs with the reasons for subsequent verification.  
The IP returned by subjects or any unused IP (that is, never dispensed to any subject) must be 
destroyed after accountability has been performed and only after written authorization from 
Karyopharm Therapeutics, Inc. has been received.  
Subject compliance with the treatment and protocol includes willingness to comply with all 
aspects of the protocol. The investigator will try to ensure complete compliance with the 
dosing schedule by providing timely instructions to the patients. In case of non-compliance, 
the patients will be instructed again. At the discretion of the principal investigator, a subject 
may be discontinued from the trial for non-compliance with follow-up visits or study drug.  
Selinexor should not be used for any purpose outside the scope of this protocol, nor may 
selinexor be transferred or licensed to any party not participating in the clinical study. Data for 
selinexor are confidential and proprietary and shall be maintained as such by the investigators. 
6.3 
Concomitant Medications and Therapies 
Concomitant medications include any prescription or over-the-counter preparation, including 
vitamins, dietary supplements, over-the-counter medications, and oral herbal preparations 
taken during the study. Patients may continue their baseline medication(s). Any diagnostic, 
therapeutic, or surgical procedure performed during the study period should be recorded, 
including the dates, description of the procedure(s), and any clinical findings, if applicable. 


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Allowed Therapy 
Any medication which is considered necessary for a subject’s welfare is permitted and may be 
given at the discretion of the investigator. Medications for treatment of underlying disease and 
symptomatic treatment of adverse events are permitted. Exceptions are listed in the section 
below. 
Use of Blood Products 
During treatment, patients may receive red blood cell (RBC) or platelet transfusions, if 
clinically indicated, per institutional guidelines.  
Appropriate anti-coagulation is allowed during the study (e.g., low molecular weight heparin, 
direct factor Xa inhibitors, etc.). Warfarin is allowed during the study provided patients are 
monitored for INR twice a week during the first two cycles of therapy, then weekly to 
biweekly. Patients may receive supportive care with erythropoietin, darbepoetin, granulocyte-
colony stimulating factor or granulocyte macrophage-colony stimulating factor, pegylated 
growth factors, and platelet stimulatory factors, in accordance with clinical practice or 
institutional guidelines prior to entry and throughout the study. 
 
Prohibited Therapy 
Concurrent therapy 
Concurrent therapy with any approved or investigative anticancer therapeutic outside of those 
included in this study is not allowed except hydroxyurea. Hydroxyurea is allowed after 
consultation with medical monitor and PI. Use of any immunosuppressive agents during the 
study must be confirmed by the Sponsor-Investigator. Treatment that could increase selinexor 
concentration should be prohibited. 
Diet 
There are no dietary restrictions on this study. Patients on selinexor should maintain adequate 
caloric and fluid intake. 
Medications 
Patients should not take glutathione (GSH)-, S-adenosylmethionine (SAM)-, or N-
acetylcysteine (NAC)-containing products during their participation in this study as these 
products may enhance the metabolism of selinexor. However, they are permitted if the patient 
has elevated liver function tests. 
Given the theoretical potential for GSH depletion, the total dose of acetaminophen should be 
≤ 1 gram per day on days of selinexor dosing. 
6.4 
Duration of Therapy 
Study subjects may remain on treatment until they experience intolerable toxicities, stop 
receiving clinical benefit in the opinion of the investigator, or experience IWG-MRT disease 
progression. Patients who experience IWG-MRT disease progression may continue treatment 
at the discretion of the investigator if they meet any of the following criteria:  
• Subjects are continuing to receive clinical benefit (i.e. symptom 
improvement and/or anemia response). 


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• Subject meets progression criteria based solely on spleen size without 
leukemic transformation (appendix 5). 
 
 
Criteria for Discontinuation of Study Intervention 
In addition to the drug-specific discontinuation criteria listed in section 7.2, the following will 
result in treatment discontinuation: 
• Subject withdraws consent from the study treatment and/or study procedures. A 
subject must be removed from the trial at his/her own request. At any time during the 
trial and without giving reasons, a subject may decline to participate further. The 
subject will not suffer any disadvantage as a result. 
• Any AE that requires a dose interruption > 28 days. 
• Unacceptable AE or toxicity that cannot be managed by supportive care. 
• Other AEs or intercurrent illnesses which, in the opinion of the investigator, would be 
injurious to the health or well-being of the subject and warrant their withdrawal from 
study treatment. 
• Necessity for prohibited treatment (as defined in section 6.3) of sufficient dose and 
duration to confound the study results. 
• Sexually active subjects who refuse to use medically accepted barrier methods of 
contraception (as defined in section 7.4) during the course of the study and for 3 
months after discontinuation of study treatment. 
• Women who become pregnant or are breastfeeding. 
• Significant non-compliance with the protocol schedule or treatment in the opinion of 
the investigator.  
• Subject is lost to follow-up or dead. 
• Request by regulatory agencies for termination of treatment of an individual subject or 
all subjects under the protocol. 
Any patient who does not withdraw from the study but who stops attending study visits and 
does not respond to 3 documented contact attempts will be considered lost to follow-up. 
All patients will be followed until disease progression, withdrawal of consent, occurrence of 
any withdrawal criteria, loss of clinical benefit or intolerable toxicity precluding further 
treatment with study treatment, death or loss to follow up. 
 
Criteria for Withdrawal from the Study 
Subjects will be taken off study for the following: 
• Completed study follow-up period 
• Participant requests to be withdrawn from study 
• Death 


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• Screen failure 
• The study is discontinued at the discretion of the PI or drug manufacturer for any 
reason, including medical or ethical reasons affecting the continued performance of the 
study, or difficulties in the recruitment of patients 
 
7 
TOXICITIES AND DOSAGE MODIFICATION 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for adverse event and serious adverse event reporting.  
While drug-related major organ toxicities are not prominent, selinexor treatment can lead to a 
number of constitutional and other side effects. Therefore, patients should be treated aggressively 
with supportive care to reduce toxicities and prevent the need for dose modifications. 
Based on preliminary observations from the ongoing Phase 1 studies in patients with advanced 
hematological and solid tumors, selinexor shows a reasonably wide therapeutic range with 
activity observed at doses ranging from ~6 mg/m2 to ≥ 60 mg/m2 (approximately 10 mg to 120 
mg orally).  
Therefore, in order to optimize specific anti-tumor activity and tolerability, dose modifications 
and treatment delays will be allowed as described below. Each dose modification or treatment 
delay must be documented (including the reason for the modification or delay).  
7.1 
Dose Modifications 
For patients enrolled after protocol version 7, alternate dosing schedules, dose reductions, 
and/or treatment delays in response to AEs are allowed as defined in Table 3 below.  
Dose interruptions are due to non-resolving adverse events lasting > 28 days are prohibited 
and will result in permanent discontinuation from treatment. 
Refer to Section 7.2 and Table 4 for dose reduction and interruption recommendations for 
specific AEs.  
Table 3: Pre-specified Dose Modifications for AEs Related to Selinexor 
 
Dose Level 
Dose of Selinexor  
Dose Escalation 
1 
60 mg once weekly 
Starting Dose 
0 
40 mg once weekly 
Dose reduction 
-1 
20 mg once weekly 
Dose escalation for selinexor is allowed after 12 weeks if no grade 2 or higher weight loss 
occurred. Dose escalation is at the discretion of the treating physician and requires 
documented consultation with the PI and medical monitor.  
7.2 
Guidelines for Management of Adverse Events 
Patients who are experiencing tolerable low-grade symptoms and are deriving clinical benefit 
from selinexor treatment may receive a dose reduction at the discretion of the enrolling 


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physician and after consultation with the PI (with subsequent re-escalation allowed as 
described in Section 7.1). Of note, the constitutional side effects associated with selinexor 
often attenuate over the first 4 to 6 weeks of treatment; nearly all are reversible with dose 
modification and/or supportive care. 
Supportive care per institutional guidelines and/or National Comprehensive Cancer Network® 
Clinical Practice Guidelines in Oncology (NCCN) should be used as clinically indicated at the 
discretion of the treating physician.  
Prophylactic therapy with 5-HT3 antagonists or other anti-nausea agents prior to each dose 
and as needed thereafter is required for all patients initiating selinexor treatment. Additional 
anti-nausea agents such as olanzapine, dopamine 2 antagonists, neurokinin 1 receptor 
antagonists, or others should be considered in any patients with insufficient response to initial 
therapy.  
Particular attention should be also paid to anorexia with poor caloric intake which is often 
accompanied by poor fluid intake. This can lead to weight loss, dehydration, and fatigue. 
Nutritional consultation, frequent body weight assessments, and appetite stimulants (e.g., 
olanzapine or megesterol acetate) can mitigate anorexia and weight loss. 
Some patients with rapid tumor responses experience significant fatigue, nausea, malaise 
and/or asthenia after 1 or more doses of selinexor. This effect has not been associated with 
typical markers of tumor lysis syndrome, but if suspected, assessment of tumor response is 
strongly recommended in order to better inform treatment recommendations. 
Thrombocytopenia  
Selinexor may induce reductions in platelet counts, with minimal effects on numbers of 
megakaryocytes. The effects of selinexor on platelet generation are related to a slowing of 
maturation of megakaryocytes and a reduction in their average ploidy. There is no known 
effect on platelet function, and bleeding associated with low platelets has been uncommon.  
Interruption of selinexor therapy, when appropriate, may lead to return of platelet counts in 1 
to 3 weeks. See Table 4 for specific guidance for managing Grades 1 through 4 
thrombocytopenia. Thrombopoietin agonists, particularly romiplostim at moderate to high 
doses, have improved platelet counts in heavily pretreated patients receiving selinexor, permitting 
continued dosing and maintaining anti-neoplastic effects. 
Neutropenia  
Standard granulocyte growth factors are highly effective for the treatment of neutropenia 
observed during treatment with selinexor and should be used early in patients whose 
neutrophil counts decline during treatment. Patients should be instructed to report any 
symptoms or signs of infection such as fever, pain, sweating, and redness to their physician 
immediately. If infection during neutropenia is suspected, then standard treatment for febrile 
neutropenia may be instituted. Selinexor should be interrupted until the patient is clinically 
stable on appropriate antimicrobial agents. No known interactions with selinexor and 
antimicrobial agents have been reported, and selinexor may be restarted when the patient’s 
condition has clinically stabilized.  
Anemia  


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Selinexor-induced anemia may contribute to dizziness, confusion, syncope and/or fatigue, 
particularly in elderly patients and patients who are at greater risk of cognitive sequelae. As 
per NCCN Guidelines, treatment with red blood cell (RBC) transfusions and/or growth 
factors, per institutional guidelines, should be considered for patients with symptomatic 
anemia. 
Nausea 
In order to minimize nausea, all patients should receive 5-hydroxytryptamine (5-HT3) 
antagonists (8 mg or equivalent) unless contraindicated, starting on C1D1 before the first dose 
of study treatment and continued 2 to 3 times daily, as needed. Additionally, olanzapine (2.5 
mg or higher) may be given prior to the first dose of selinexor and continued once daily (QD), up 
to 4 days, as per NCCN Guidelines. Patients with breakthrough nausea or vomiting should receive 
additional anti-emetic agents.  
Infection 
No prophylactic antimicrobial agent is recommended for most patients initiating therapy with 
selinexor. Patients with a history of recurrent infections or those at high risk for specific 
infections may continue their prophylactic antimicrobial regimens without modification when 
initiating selinexor therapy.  
 
Selinexor should be withheld in patients with suspected or active uncontrolled infections, 
grade 4 infections, or clinical sepsis (in the absence of documented infection). Selinexor 
treatment can be resumed after initiation of appropriate antimicrobial therapy and when the 
infection has clinically resolved and/or the patient is clinically stable. When ready to resume 
selinexor, treatment may continue at the original dose, even in the setting of continued 
antimicrobial agents.  
Diarrhea  
Diarrhea associated with selinexor is typically watery and low-grade and usually responds to 
treatment with standard anti-diarrheal agents (e.g., loperamide) and/or dose modification. 
Careful assessment of the patient’s volume status is essential. Fluid replacement is important 
to prevent dehydration, fatigue and electrolyte abnormalities (e.g., hyponatremia).  
Fatigue  
Prevention of anorexia, vomiting, and dehydration may reduce fatigue. Also, as per NCCN 
Guidelines, the use of methylphenidate 5 mg QD each morning may be helpful. Hemoglobin 
levels must be optimized as anemia appears to contribute substantially to fatigue, particularly 
in patients with heavily pretreated hematologic malignancies. In patients with adequate 
antitumor control on selinexor, QW dosing is often associated with improvement in fatigue 
and other side effects.  
Decreased Appetite  
In patients with problematic food/liquid/caloric intake secondary to anorexia, a patient log of 
food and drink, as well as body weights, should be considered and monitored by site staff. 
Nutritional counseling is important. Dysgeusia may contribute to the anorexia, and dietary 


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adjustments can be helpful. Fresh juices and simple carbohydrates, as well as ginger-
containing foods and beverages, can improve appetite; ginger-containing foods may also 
improve dysgeusia. Administration of high caloric beverages (e.g., Boost®, Ensure®) and 
appetite stimulating agent(s) should be instituted aggressively in patients who develop 
significant anorexia.  
A combination of appetite stimulating agents, particularly olanzapine (2.5 to 5.0 mg every 
morning), and standard anti-emetics is usually effective in managing selinexor associated 
anorexia that does not respond to the above interventions. Megesterol acetate 400 mg daily 
may also be effective. Additional information on the management of anorexia is provided in 
the NCCN Guidelines. 
Hyponatremia  
Investigators should rule out the possibility of pseudo-hyponatremia due to elevated glucose 
(or monoclonal protein) levels. Abnormal serum sodium levels should be corrected. Adequate 
fluid and caloric intake, including electrolyte-rich beverages instead of plain water, has led to 
reversal of hyponatremia. Diuretic use should be addressed and possibly stopped, and salt 
supplements should be considered if hyponatremia persists 
Confusional State  
Confusion is usually multifactorial with associated events including older age, dehydration, 
electrolyte abnormalities, anemia, diarrhea, infection, concomitant medications, other 
comorbidities and/or high tumor burden. Optimization of fluid status, electrolytes, 
hemoglobin levels, thyroid function, and concomitant medications should be undertaken. 
Glucocorticoids should be suspected and splitting the glucocorticoid dose over 2 days may be 
helpful. Other CNS-active agents should also be evaluated. However, confusion can be an 
isolated and dose-dependent event and thus a direct role for selinexor, which crosses the blood 
brain barrier, cannot be ruled out. Dose reduction of selinexor may be undertaken when other 
causes have been ruled out. If confusion resolves and patient returns to at least baseline status, 
cautious re-escalation of selinexor may be attempted. 
Renal Insufficiency 
Baseline renal insufficiency does not appear to affect tolerability of selinexor and renal 
dysfunction should not preclude continued dosing with selinexor, even for patients on 
dialysis. If a patient is undergoing dialysis, selinexor should be given after the dialysis 
procedure because the effect of dialysis on selinexor plasma levels has not yet been studied. 
Selinexor can lead to increased creatinine, and the majority of these cases are associated with 
hypovolemic conditions (i.e., represent “pre-renal” azotemia). Dose modifications or 
interruptions and appropriate hydration typically reverse the increased creatinine. 
Vision Blurred and Cataracts  
Patients reporting blurry vision or other visual changes should be evaluated by an 
ophthalmologist. Nearly all cases of treatment-emergent visual changes have not been 
associated with objective findings. Changes in lens prescriptions and/or wetting drops may 
improve vision. Blurred vision associated with selinexor use is typically self-limited, and 
dosing can usually be maintained at the same level and frequency.  


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Patients who are at risk of cataract formation, or have cataracts present at baseline, should be 
monitored for changes in lens opacity. If changes in lens opacity are observed, the patient 
should be evaluated by an ophthalmologist. In selinexor clinical studies, several patients have 
undergone cataract surgery with minimal to no interruption of selinexor dosing and without 
complications.  
The relationship between cataract and selinexor is confounded by multiple contributing 
factors which are known risk factors for cataracts: the heavily pretreated nature of the 
patients’ cancers, older age, pre-existing lens disease, and concomitant (and prior) 
medications including glucocorticoids.  
The incidence and severity of occurrence of ocular AEs following treatment with selinexor was 
evaluated in a large, pooled-population of patients treated in all CSTs (N = 1458). These results 
show that new onset, clinically significant ophthalmological abnormalities following initiation of 
selinexor treatment were not commonly associated with objective findings upon ophthalmological 
examination 
Tumor Lysis Syndrome  
Tumor lysis syndrome (TLS) is rarely observed in patients treated with selinexor (see Section 
5.5.2.3.1). It has been reported in 5 patients with MM, 2 patients with ALL, and 1 patient with 
AML. It has not been reported in any patient with NHL or solid tumor to date. All protocols 
require assessment of relevant screening laboratories and patient status (e.g., adequate 
hydration) to mitigate the risks for TLS.  
Early recognition of signs and symptoms in patients at risk for TLS, including identification 
of abnormal clinical and laboratory values, is key and Investigators must ensure that patients 
being treated with selinexor maintain adequate caloric and fluid intake. Close monitoring and 
management of patients with hematological malignancies, including MM, for potential signs 
and symptoms of TLS are most relevant.  
Based on the data received during the interval, evidence of a causal relationship between TLS 
and selinexor is not available at this point. Hence, it will remain as an important potential risk 
and Karyopharm will continue to monitor this event.  
Overdose 
As selinexor is metabolized by glutathione (GSH) conjugation, it is possible, but not 
demonstrated, that hepatic GSH depletion might occur in case of extreme overdose. 
Therefore, in patients who develop liver function test abnormalities, supportive measures such 
as S-adenosylmethionine (SAM) or other drugs that can replace GSH might be considered as 
part of the overall management plan. 
Management guidelines for other selinexor-related AEs are provided in Table 4 below. 


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Table 4: Supportive Care and Selinexor Dose Adjustment Guidelines for AEs related to 
Selinexora,b,c 
Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Fatigue  
Grade 1 
Maintain dose. Rule out other causes. If found to be anemic and 
symptomatic, consider transfusing even with hemoglobin >8 g/dL (anemia 
Grade <3). 
Patients with significant fatigue after several doses of selinexor may have 
an antitumor response. Consider an unscheduled assessment of tumor 
response as part of the patient’s evaluation.  
Grade 2 lasting ≤7 days 
As per the NCCN guidelines, consider stimulants such as methylphenidate 
5mg QD in the morning only. 
Grade 2 lasting >7 days or 
Grade 3 
Rule out other causes. If found to be anemic and symptomatic, consider 
transfusions for hemoglobin >8 g/dL (Grade <3); transfusions usually 
indicated for Hb <8 g/dL (Grade ≥3). Interrupt selinexor dosing until 
resolved to Grade 1 or baseline.  
For first occurrence, restart selinexor at current dose.  
For ≥ second occurrence, reduce selinexor by 1 dose level. 
Patients with significant fatigue after several doses of selinexor may have 
an antitumor response. Consider an unscheduled assessment of tumor 
response as part of the patient’s evaluation. 
As per the NCCN guidelines, consider stimulants such as methylphenidate 
5mg QD in the morning only. 
Anorexia or Weight loss 
Grade 1 anorexia 
Maintain dose. Rule out other causes. Consider nutritional consultation and 
use nutritional supplements (e.g., Ensure®, Boost®). 
For persistent symptoms, start appetite stimulants, such as olanzapine (2.5 
to 5 mg PO every morning) or megesterol acetate (400 mg QD), per NCCN 
guidelines. 
Grade1 weight loss  
Grade 2 anorexia 
Initiate appetite stimulants, such as olanzapine (2.5 to 5 mg PO every 
morning) or megesterol acetate (400 mg QD), as per NCCN guidelines. 
Grade 2 weight loss 
Grade 3 anorexia,  
or Grade 3 weight loss 
Interrupt selinexor dosing until improved to Grade 1 or baseline and weight 
stabilizes. Reduce selinexor by 1 dose level. 
Rule out other causes. Consider nutritional consultation and use nutritional 
supplements (e.g., Ensure®, Boost®)  
Start appetite stimulants as above 
Grade 4 anorexia 
Permanently discontinue selinexor 


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Nausea, Acute  
Grade 1 or 2 
 
Maintain dose. Rule out other causes. Use standard additional anti-nausea 
medications to supplement the protocol-required 5-HT3 antagonists. 
If persistent, use additional anti-nausea medications to supplement the 
protocol-required 5-HT3 antagonist(s). Olanzapine 2.5 to 5 mg PO every 
morning, per NCCN guidelines, can mitigate nausea and anorexia. 
Grade 3 
Rule out other causes. Use additional anti-nausea medications to 
supplement the protocol-required 5-HT3 antagonist(s). Olanzapine 2.5 to 
5 mg PO every morning, per NCCN guidelines, can mitigate nausea and 
anorexia. 
Interrupt selinexor dosing until resolved to Grade ≤2 or baseline and reduce 
selinexor by 1 dose level.  
Patients with significant nausea/vomiting after several doses of selinexor 
may have an antitumor response. Consider an unscheduled assessment of 
tumor response as part of the patient’s evaluation. 
Hyponatremia  
Grade 1 (sodium levels < Normal to 
130 mmol/L)  
Maintain dose. Rule out other causes including drug (e.g., diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150 mg/dL).  
Treat hyponatremia per institutional guidelines including dietary review. 
Provide supplemental oral and/or intravenous fluids if dehydration is 
present. Consider addition of salt tablets to patient’s diet. 
Grade 3 with sodium levels 
<130-120 mmol/L without 
symptoms  
Rule out other causes including drug (e.g., diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150 mg/dL).  
If (corrected) sodium is Grade ≤3 and continues to be asymptomatic, then 
patient may continue current dosing without interruption provided that IV 
saline and/or salt tablets are provided and patient is followed closely.  
If Grade 3 is persistent or worsens or does not respond to treatment, 
interrupt selinexor dosing until resolved to Grade 1 or baseline and reduce 
selinexor by 1 dose level. 
Grade 3 with sodium levels 
<130-120 mmol/L with symptoms 
or Grade 4 (<120 mmol/L) 
Rule out other causes including drug (e.g., diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose > 150 mg/dL).  
Interrupt selinexor dosing until resolved to Grade 1 or baseline and without 
symptoms. Reduce selinexor by 1 dose level. 
Diarrhea  
Grade 1 
Maintain dose. Rule out other causes including drug effects. Treat per 
institutional guidelines with anti-diarrheals, such as loperamide. 
Grade 2 
Rule out other causes including drug effects. Treat per institutional 
guidelines with anti-diarrheals. Interrupt selinexor dosing until resolved to 
Grade 1 or baseline.  
For first occurrence, restart selinexor at current dose.  
For ≥ second occurrence, reduce selinexor by 1 dose level. 
Grade 3   
Interrupt selinexor dosing until resolved to Grade 1 or baseline and patient 
is clinically stable. Reduce selinexor dose by 1 dose level. 
Grade 4 
Permanently discontinue selinexor 
Thrombocytopenia 
Grade 1 or 2 
Maintain dose. Rule out other causes including drug effects. 
Grade 3 without bleeding 
Maintain dose. Rule out other causes including drug effects.  


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Grade 4 without bleeding 
Rule out other causes including drug effects. Platelet transfusion is allowed 
if clinically indicated at the discretion of the principal investigator.  
For first occurrence: skip 1 dose and reduce selinexor by 1 dose level. 
If recurrent, the investigator in consultation with the Medical Monitor may 
decide to continue selinexor dosing without dose reductions and/or 
interruptions as specified above, provided that platelet counts and bleeding 
symptoms/signs are closely monitored. Treatment with moderate to high 
doses of thrombopoietin stimulating agents such as romiplostim 5 to 
10 µg/kg SC weekly or eltrombopag 100 to 150 mg QD can be considered 
at the discretion of the principal investigator. Platelet transfusion is allowed 
if clinically indicated at the discretion of the principal investigator.  
 
Grade ≥3 with bleeding 
 
Interrupt selinexor dosing and check platelet counts weekly until the 
bleeding has stopped, patient is clinically stable and the platelets have 
recovered to Grade ≤3 or baseline. Platelet transfusion is allowed if 
clinically indicated at the discretion of the principal investigator. When 
resuming selinexor, reduce by 1 dose level. 
If recurrent, unless contraindicated, start treatment with moderate to high 
doses of thrombopoietin stimulating agents as above. 
Neutropenia 
Grade 4 neutropenia (afebrile)  
OR 
Febrile neutropenia 
Institute colony stimulating factors and prophylactic antibiotics as 
clinically indicated per institutional guidelines. 
Interrupt selinexor and check neutrophils at least weekly until recovers to 
Grade 3 or baseline and without fever (if febrile) and the patient is 
clinically stable. Colony stimulating factors per institutional guidelines or 
at the discretion of the principal investigator. When resuming selinexor, 
reduce by 1 dose level. 
If recurrent, continue colony stimulating factors, interrupt selinexor until 
neutrophil counts improve to Grade ≤3 or baseline levels. Investigator in 
consultation with the Medical Monitor may decide to continue selinexor 
dosing without dose reductions as specified above, provided that CBC and 
infection symptoms/signs are closely monitored. 
Anemia 
Treat per institutional guidelines including blood transfusions and/or erythropoietins. Consider transfusing for 
symptoms with hemoglobin >8 g/dL (Grade <3) or for any Grade 3 (hemoglobin <8 g/dL). If possible, maintain 
selinexor dose as long as patient is clinically stable, but if a dose reduction or interruption is desired, it should be 
done at the discretion of the treating physician and requires authorization from the principal investigator and 
consultation with the medical monitor if indicated. 
Other clinically significant selinexor-related adverse events 
Grade 1 or 2 
Rule out other causes. Maintain dose. Start treatment and/or standard 
supportive care per institutional guidelines. 
Grade 3 
Rule out other causes. Interrupt selinexor until recovers to Grade 2 or 
baseline and reduce selinexor by 1 dose level. 
Isolated values of Grade 3 alkaline phosphatase do NOT require dose 
interruption. Determination of liver versus bone etiology should be made, 
and evaluation of gamma-glutamyl transferase, 5'-nucleotidase, or other 
liver enzymes should be performed. 
Grade 4 
Permanently discontinue selinexor 
aFor all Grade ≥3 hematologic or Grade 3 non-hematologic AEs that are NOT selinexor related, after consultation 
with the principal Investigator, selinexor, dosing may be maintained. 


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bFor all selinexor-related AEs, if the below prescribed dose reductions/interruptions result in a stabilization of 
≥4 weeks, a re-escalation may be considered at the discretion of the treating physician, and consultation with the 
medical monitor if indicated, and requires authorization from the principal investigator.  
All dose modifications should be based on the worst preceding toxicity. 
cFor all Grade 4 non-hematologic AEs that are NOT selinexor related, selinexor should be permanently discontinued. 
Note: When toxicities due to selinexor have returned to baseline levels or the patient has stabilized, the dose of 
selinexor may be re-escalated at the discretion of the treating physician, and consultation with the medical monitor if 
indicated, and requires authorization from the principal investigator.  
 
Conditions Not Requiring Selinexor Dose Reduction 
The following conditions are exceptions to the dose-modification guidelines and do not 
require a dose reduction or delay: 
• Alopecia of any grade 
• Electrolyte or serum analyte (e.g., urate) abnormalities that are reversible with 
standard interventions 
• Isolated values of Grade ≥ 3 alkaline phosphatase. Determination of liver versus bone 
etiology should be made, and evaluation of gamma-glutamyl transferase, 5'-
nucleotidase, or other liver enzymes should be performed. 
In addition, selinexor dosing may be maintained in case of grade ≥ 3 hematological or non-
hematological AEs not listed above (in Section 7.2) at the discretion of the enrolling physician 
and after consultation with the Sponsor-Investigator and the DSMC medical monitor. 
7.3 
Contraception 
Patients should not become pregnant or father a child while on this study as selinexor can 
affect an unborn baby.  
Female patients of childbearing potential must agree to use two methods of contraception (one 
highly effective and one effective) and have a negative serum pregnancy test at Screening 
Male patients must use an effective barrier method of contraception if sexually active with a 
female of childbearing potential.  
Highly effective methods of contraception include:  
• Hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, 
injectables, and implants)  
• Intrauterine device or intrauterine system 
• Vasectomy or tubal ligation 
Effective methods include:  
• Barrier methods of contraception (e.g., male condom, female condom, cervical cap, 
diaphragm, contraceptive sponge) 
Notes: 
• No barrier method by itself achieves a highly effective standard of contraception 
• The proper use of diaphragm or cervical cap includes use of spermicide and is 
considered one barrier method. 


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• The cervical cap and contraceptive sponge are less effective in parous women. 
• The use of spermicide alone is not considered a suitable barrier method for 
contraception. 
• When used consistently and correctly, “double barrier” methods of contraception (e.g., 
male condom with diaphragm, male condom with cervical cap) can be used as an 
effective alternative to the highly effective contraception methods described above. 
• Male and female condoms should not be used together as they can tear or become 
damaged. 
Alternatively, the following fulfill the contraception requirements: 
• A sexual partner who is surgically sterilized or post-menopausal. 
• Total (true) abstinence (when this is in line with the preferred and usual lifestyle of the 
patient), is an acceptable method of contraception.  
NOTE: periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
• The method of acceptable contraception must be explained to both male and female 
potential patients. In order to be eligible for the study, patients must agree to use the 
methods of birth control described above throughout the study and for 3 months 
following the last dose of study treatment at the time of consent for the study. 
Breastfeeding 
Women should not breastfeed while on this study.


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8 
STUDY CALENDAR  
1 cycle = 28 days (± 3 days unless otherwise specified) 
Some study visits may be conducted remotely when remote telehealth visits do not present increased risk to the participant and all 
necessary data for the trial can be collected. The method of telehealth should be documented in the participants’ charts. Visits that 
require study-related imaging, research lab samples, and/or pathology should be conducted in person.  
Activity/Assessment 
Screening 
Baseline 
Cycle 1 
Cycles 2 to 
6 
Cycle 7 27 Cycle 10 +27 
End of 
Treatment 
Visit (EOT) 
Survival 
Follow-up23 
(Every 3 
mo.) 
Day -28 to  
Day -1 
Day -7 to 
Day -1 
D1 
D322 D8 D15 
D22 
D1 
D15 
D1 
D1 
7 Days Post-
Last Dose 
± 1 day 
± 2 days 
± 2 days 
± 3 days 
± 2 days 
± 14 days 
Informed consent1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Screening symptom 
evaluation3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Height4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
X 
 
 
 
 
X 
 
X 
X 
X 
 
Body Surface Area (BSA)4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Body Mass Index (BMI)4 
X 
 
X 
 
 
 
 
X 
 
X 
X 
X 
 
Vital signs5 
X 
 
X 
 
 
 
 
X 
 
X 
X 
X 
 
Physical examination6 
X 
 
X 
 
 
 
 
X 
 
X 
X 
X 
 
DIPSS risk assessment7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status8 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
Optional Ophthalmic exam9 
X 
 
ACI 
X 
 
12-lead ECG10 
X 
 
ACI 
X 
 
CBC with differential11 
X 
X11 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 


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Activity/Assessment 
Screening 
Baseline 
Cycle 1 
Cycles 2 to 
6 
Cycle 7 27 Cycle 10 +27 
End of 
Treatment 
Visit (EOT) 
Survival 
Follow-up23 
(Every 3 
mo.) 
Day -28 to  
Day -1 
Day -7 to 
Day -1 
D1 
D322 D8 D15 
D22 
D1 
D15 
D1 
D1 
7 Days Post-
Last Dose 
± 1 day 
± 2 days 
± 2 days 
± 3 days 
± 2 days 
± 14 days 
Thyroid stimulating hormone 
(TSH) 
X 
 
ACI 
 
Complete serum chemistry12 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
Limited serum chemistry13 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
Coagulation tests14 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
MRI (or CT abdomen)15 
 
X 
 
 
 
 
 
X15 
 
X 
X15 
X15 
 
Chest radiograph16 
X 
 
ACI 
 
Serum pregnancy test17 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow and peripheral 
blood for local pathology 
review18 
X 
 
 
 
 
 
 
 
 
X 
X18 
X 
 
Bone marrow and peripheral 
blood for central pathology 
review18 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
Bone marrow aspirate for 
CD34 section and testing,  
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
Selinexor administration19 
 
 
See administration table below 
 
 
Blood draw for PDn testing20 
 
 
 
 
 
 
 
X20 
 
 
 
 
 
Adverse events 
 
 
X 
 
Concomitant medication 
 
X 
 
Nutritional consultation21 
X 
 
ACI 
 
 
Telephone contact22,23 
 
 
 
X22 
 
 
 
 
 
 
 
 
X23 
MPN-SAF TSS24 
 
X 
 
 
X 
X 
 
X 
 
X 
X 
X 
 
IWG-MRT assessment25 
 
X 
 
 
 
 
 
X25 
 
X 
X 
X 
 
Peripheral blood sample for 
cytokine profile26 
 
X 
 
 
 
 
 
X26  
X26 
 
X 
 
Peripheral blood sample for 
JAK2 V617F, MPL and 
 
X 
 
 
 
 
 
X26  
X26 
 
X 
 


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Activity/Assessment 
Screening 
Baseline 
Cycle 1 
Cycles 2 to 
6 
Cycle 7 27 Cycle 10 +27 
End of 
Treatment 
Visit (EOT) 
Survival 
Follow-up23 
(Every 3 
mo.) 
Day -28 to  
Day -1 
Day -7 to 
Day -1 
D1 
D322 D8 D15 
D22 
D1 
D15 
D1 
D1 
7 Days Post-
Last Dose 
± 1 day 
± 2 days 
± 2 days 
± 3 days 
± 2 days 
± 14 days 
CALR exon 9 mutations 
allele burden26 
 
Procedure 
Day 1 of each cycle 
Day 8 of each cycle 
Day 15 of each cycle 
Day 22 of each cycle 
Selinexor administration19 
In clinic  
In clinic for C1 
At home for C2+ 
In clinic for C1 
At home for C2+ 
At home for all cycles 
ACI = As clinically indicated 
1 
Prior to the first study-specific measures. 
2 
Review of medical history and medication history, from the 12 months before screening, but incorporating, in full, prior lines of therapy regardless of date of 
occurrence. Including details of all therapies for myelofibrosis (start/stop dates, best response, disease progression during/after therapy, discontinuations due 
to intolerability/toxicity, etc.).  
3 
Using Screening Symptoms Form, see Appendix 6 
4 
Body Surface Area (BSA) and height will be collected at screening only. Screening height will be used to calculate BMI at all future visits. 
5 
 To include blood pressure, pulse, temperature, and oxygen saturation.  
6 
All physical examinations (PE) must include spleen palpation. Symptom-directed limited PE can be performed outside of screening and EOT.  
7 
See Appendix 8 
8 
ECOG performance status assessments will be done on D1 of each Cycle, however the assessment for C1D1 may be done during Screening or pre-dose 
C1D1. 
9 
Full ophthalmic examination is optional at baseline and the final visit, and, if clinically indicated, during the study. Prior to dilation, best corrected visual -–
acuity, slit lamp examination including tonometry, following dilation; fundoscopy and slit lamp to document lens clarity – if a cataract/lens opacity is seen 
during the examination, the cataract/lens opacity will be graded according to a Grade 1-4 system (see Appendix 2) 
10 ECG will be performed during Screening (or pre-dose C1D1) and the EOT Visit and as clinically indicated throughout the study.   
11 CBC with differential includes hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, white blood cell (WBC) count, WBC differential, RBC count, lymphocytes, monocytes, neutrophils, band neutrophils, eosinophils, basophils, 
platelets. WBC differential may be automated or manual as per institutional standards. Reticulocytes may be done only when clinically indicated. The 
baseline CBC need not be repeated if the screening CBC is performed within 7 days of C1D1.  
12 Complete serum chemistry includes limited serum chemistry (as defined below) as well as, phosphate, magnesium, LDH, amylase, lipase, and uric acid. It is 
due at Screening or C1D1, then D1 of each subsequent Cycle, and EOT visit.   


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13 Limited chemistry includes sodium, potassium, chloride, calcium, bicarbonate, BUN, creatinine, glucose, total protein, albumin, ALT, AST, alkaline 
phosphatase, and total bilirubin. It is due at C1D8 and C1D15.  
14 Includes prothrombin time (PT), international normalization ratio (INR), and activated partial thromboplastin time (aPTT). 
15 Spleen volume will be measured by MRI (or CT abdomen if MRI is contraindicated) at screening, at C4D1 after completion of 3 cycles and at C7D1 after 
completion of 6 cycles, allowing up to 4 weeks after cycle 7 D1. Additional MRIs will be performed for patients continuing on study treatment at cycle 10 
D1, cycle 13 D1, cycle 19 D1, C25D1 to assess spleen volume. Imaging modality should remain consistent throughout study for each patient. Screening 
MRI should be completed ≤14 days prior to C1D1. An additional MRI will be performed at the End of Treatment for all patients including those who do not 
complete at least 6 cycles of study treatment unless death occurs. CT abdomen is acceptable if MRI is contraindicated for estimation of spleen volume. 
16 Both posteroanterior and lateral films should be obtained at baseline. Note that this test does not need to be repeated if results are available from a test 
performed within 30 days prior to start of therapy. This test serves as a baseline in the event that patients develop any adverse events during the study. 
17 For women of childbearing potential; negative serum β-hCG pregnancy test within 3 days of C1D1. 
18 Bone marrow biopsies and aspirates will be obtained at ≤ 42 days before C1D1, C7D1 (± 7 days), and EOT. Additional bone marrow biopsies will be 
performed at C19D1 and then every 12 cycles after that until treatment discontinuation. 
19 Study drug administration will take place on a weekly basis and will be done in clinic at C1D1, and on the first day of each subsequent cycle. Patients will be 
instructed to take their dose of study drug at home on D8, D15, and D22 of each subsequent cycle.  
20 Blood draws for PDn analysis will be collected at either C2D1 or C3D1 pre-dose (within 10 minutes prior to dose) and 4 hours post-dose (± 10 min) 
21 It is strongly recommended that patients be given nutritional consultation to discuss food recommendations and strategies for managing potential nausea and 
appetite changes experienced with selinexor. Nutritional consultation can be done by study nurse/clinician face-to-face or by the HCI Wellness Center or site 
equivalent or over the telephone. These consultations should be continued during study therapy as clinically indicated.  
22 Telephone call (or visit) with patient to evaluate supportive care medications and adverse events, and to adjust supportive care as appropriate. The telephone 
contact with the patient must take place on Day 3 (± 1 day) following the C1D1 selinexor dosing. If available, survival follow up data may be collected from 
patient medical record review in lieu of a telephone call. 
23 After study discontinuation, a telephone call will be made to the patient (or the patient’s family) every 3 months to inquire about the patient’s disease status, 
well-being, and information on any antineoplastic therapies utilized since discontinuation of selinexor study treatment until 24 months after initiation. If 
available, survival follow up data may be collected from patient medical record review in lieu of a telephone call  
24 MPN SAF TSS evaluation will be performed at baseline and at each subsequent clinic visit (C1D8, C1D15, C2D1 and D1 of every subsequent cycle up to 
cycle 7 and every 3 cycles thereafter and EOT. Patients will be given copies of the evaluation form for time points which do not coincide with a study visit 
and will be asked to return the forms at their next visit.  
25 Disease status and/or response by IWG-MRT will be assessed at C4D1, C7D1, C10D1, C13D1, C19D1, C25D1 and EOT.  
26 Peripheral blood sample for cytokine profile, mutation allele burden will be collected at baseline, C4D1, C7D1, and at the EOT visit. 
27 Starting with Cycle 7, patients only need to return to clinic every three months unless earlier follow up is necessary per treating physician’s discretion. 
 
 


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9 
STUDY PROCEDURES 
Some study visits may be conducted remotely when remote telehealth visits do not present 
increased risk to the participant and all necessary data for the trial can be collected. The method 
of telehealth should be documented in the participants’ charts. Visits that require study-related 
imaging, research lab samples, and/or pathology should be conducted in person.  
 
9.1 
Screening Evaluations 
All screening procedures must be completed ≤ 28 days of C1D1. Screening procedures 
include: 
• Informed consent 
• Demographics 
• Inclusion and exclusion criteria 
• Review of medical history and medication history, from the 12 months before screening, 
but incorporating, in full, prior lines of therapy regardless of date of occurrence.  
• Vital signs, height, weight, BSA, and BMI 
• Physical examination including spleen size by palpation 
• ECOG performance status (Appendix 1) 
• DIPSS risk assessment (Appendix 8) 
• Screening symptoms assessment (Appendix 6) 
• Nutritional consult 
• Optional Ophthalmologic exam (Appendix 2) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated) 
o Complete serum chemistry to include:  
 CMP: sodium, potassium, chloride, carbon dioxide, alkaline phosphatase, AST, 
ALT, BUN, glucose, creatinine, calcium, total protein, albumin, total bilirubin 
(direct and indirect bilirubin must be obtained if total bilirubin is ≥ 1.5 × ULN) 
 Phosphorus, magnesium, uric acid, LDH, amylase, lipase 
o Thyroid stimulating hormone 
o Coagulation tests to include PT, INR, and aPTT 
• Serum pregnancy test (for women of childbearing potential, see Section 7.4)  
• 12-lead ECG  
• Chest X-ray  
• Bone marrow biopsy and aspiration ≤ 42 days before cycle one day one (can also be 
performed during the baseline visit). The study team will follow instructions in the lab 
manual for shipping tissue for central review. 
• Standard of care procedures (e.g., blood count, serum chemistry) performed during this 
period should not be repeated and will be used for study purposes. 


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9.2 
Baseline Evaluations 
All baseline procedures must be completed ≤ 7 days of C1D1. Baseline procedures include: 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated) – does not need 
to be repeated if screening CBC test has been performed within that same timeframe. 
o Serum pregnancy test ≤ 72 hours prior to treatment initiation (for women of 
childbearing potential, see Section 7.4) – does not need to be repeated if screening 
pregnancy test has been performed within that same timeframe. 
• MRI (or CT abdomen if MRI is contraindicated) ≤14 days of C1D1 for estimation of 
spleen volume. Imaging modality should remain consistent throughout study for each 
patient. 
• IWG-MRT assessment. 
• MF symptom burden evaluation using the MPN-SAF TSS questionnaire (Appendix 7) 
• Peripheral blood samples for cytokine profiling 
• Peripheral blood samples for evaluation of JAK2, MPL, and CALR mutant allele burden 
 
9.3 
On Treatment Evaluations 
 
Cycle 1 Day 1 
• Concomitant medication review  
• Vital signs, weight, BMI 
• Physical examination including spleen size by palpation 
• Selinexor dosing (level 0) 
 
Cycle 1 Day 3 
• Telephone call (or visit) to evaluate and/or adjust supportive care medications and 
adverse events 
 
Cycle 1 Days 8 and 15 
• Adverse events assessment and concomitant medication review 
• Laboratory assessments: 
o Limited serum chemistry to include a CMP as defined in Section 9.1  
o CBC with differential (including reticulocytes if clinically indicated)  
• MF symptom burden evaluation using the MPN-SAF TSS questionnaire (Appendix 7) 
• Selinexor dosing (patients will be instructed to take their C1D8, C1D15, and C1D22 
selinexor dose at home) 
 
Cycle 1 Day 22 
• Selinexor dosing (at home) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated)  


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Cycle 2 Day 1 – Cycle 6 Day 1 
• Adverse events assessment and concomitant medication review 
• Vital signs, weight, BMI 
• Physical examination including spleen size by palpation 
• ECOG performance status (see Appendix 1) 
• Optional Ophthalmologic exam (Appendix 2) as clinically indicated 
• MF symptom burden evaluation using the MPN-SAF TSS questionnaire (Appendix 7) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated) 
o Complete serum chemistry as defined in Section 9.1  
• Peripheral blood sample for PDn analysis pre-dose and 4 hours post-dose (± 10 min) at 
either C2D1 or C3D1. 
• Spleen volume will be measured by MRI (or CT abdomen if MRI is contraindicated) at 
the completion of 3 cycles and 6 cycles, allowing up to 4 weeks after cycle 7 D1. Imaging 
modality should remain consistent throughout study for each patient. Screening MRI 
should be completed ≤14 days prior to C1D1. 
• 12-lead ECG as clinically indicated 
• Selinexor dosing  
 
Day 8 and 22 of each cycle from Cycle 2 through Cycle 6 (not clinic visit days) 
• Selinexor dosing (at home) 
 
Day 15 of each cycle from Cycle 2 through Cycle 6 
• Selinexor dosing (at home) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated)  
9.4 
Cycle 7 Day 1 
• Adverse events assessment and concomitant medication review 
• Vital signs, weight, BMI 
• Physical examination including spleen size by palpation 
• ECOG performance status (see Appendix 1) 
• Optional Ophthalmologic exam (Appendix 2) as clinically indicated 
• Bone marrow biopsy and aspiration: local testing for pathology reporting takes sample 
priority. However, when possible bone marrow biopsy and aspirate samples should be 
taken for correlative tests per Section 14.1.1. The study team will follow instructions in 
the lab manual for shipping tissue for central review. 
• MF symptom burden evaluation using the MPN-SAF TSS questionnaire (Appendix 7) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated) 
o Complete serum chemistry as defined in Section 9.1  


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• MRI (or CT abdomen if MRI is contraindicated) for estimation of spleen volume. 
Imaging modality should remain consistent throughout study for each patient. 
• IWG-MRT response assessment. 
• 12-lead ECG as clinically indicated 
• Selinexor dosing  
• Peripheral blood samples for cytokine profiling 
• Peripheral blood samples for evaluation of JAK2, MPL, and CALR mutant allele burden 
  
Starting with cycle seven, patients will need to return to clinic every three months. 
 
9.5 
Cycle 10 + (every three months) 
• Adverse events assessment and concomitant medication review 
• Vital signs, weight, BMI 
• Physical examination including spleen size by palpation 
• ECOG performance status (see Appendix 1) 
• Optional Ophthalmologic exam (Appendix 2) as clinically indicated 
• MF symptom burden evaluation using the MPN-SAF TSS questionnaire (Appendix 7) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated) 
o Complete serum chemistry as defined in Section 9.1  
• 12-lead ECG as clinically indicated 
• Selinexor dosing  
• MRI (or CT abdomen if MRI is contraindicated) and IWG-MRT assessments will be 
performed for patients continuing on study treatment at cycle 10 D1, cycle 13 D1, and 
then every 6 cycles thereafter until treatment discontinuation to assess spleen volume and 
disease status.  
 
9.6 
End of Treatment Evaluations 
The end of treatment visit will take place 7 days (+ 2 days) after the last dose of study drug 
and will include the following: 
• Adverse events assessment and concomitant medication review 
• Vital signs, weight, BMI  
• Physical examination including spleen size by palpation 
• ECOG performance status (see Appendix 1) 
• Optional Ophthalmologic exam (Appendix 2) 
• Laboratory assessments: 
o CBC with differential (including reticulocytes if clinically indicated) 
o Complete serum chemistry as defined in Section 9.1 


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o Coagulation tests to include PT, INR, and aPTT 
• MRI (or CT abdomen if MRI is contraindicated) for estimation of spleen. Imaging 
modality should remain consistent throughout study for each patient. MRI need not be 
repeated at the EOT visit if one has been performed ≤ 6 weeks 
• IWG-MRT assessment 
• 12-lead ECG 
• MF symptom burden evaluation using the MPN-SAF TSS questionnaire (Appendix 7) 
• Bone marrow biopsy and aspiration: local testing for pathology reporting takes sample 
priority. However, when possible bone marrow biopsy and aspirate samples should be 
taken for correlative tests per Section 14.1.1. The study team will follow instructions in the 
lab manual for shipping tissue for central review. 
• Peripheral blood samples for cytokine profiling 
• Peripheral blood samples for evaluation of JAK2, MPL, and CALR mutant allele burden 
  
9.7 
Survival Follow Up 
After treatment discontinuation, a telephone call will be made to the patient (or the patient’s 
family) every 3 months to inquire about the patient’s myelofibrosis disease status, general 
health, and information on any subsequent therapies utilized since discontinuation of study 
treatment for 24 months since the initiation of treatment. If available, medical records may be 
reviewed in lieu of a telephone call to the patient. 
10 
CRITERIA FOR EVALUATION AND ENDPOINT 
10.1 
Safety 
Routine safety and tolerability will be evaluated from the results of reported signs and 
symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory 
test results. More frequent safety evaluations may be performed if clinically indicated or at 
the discretion of the investigator.  
Physical Examination 
Complete and symptom-directed physical examinations will be performed by a licensed 
physician (or physician’s assistant or nurse practitioner). 
Vital Signs 
Vital signs (blood pressure, pulse rate, and temperature) will be obtained. Height, weight, and 
BMI will be obtained. ** Note: Height will be collected at the screening visit only. Screening 
height will be used to calculate BMI at all future visits. 
 
Safety Laboratory Determinations 
Laboratory evaluations will be performed as noted in the Study Calendar. 


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10.2 
Efficacy 
 
Radiographic Assessment of Efficacy  
Volumetric measurements of the spleen will be obtained by MRI (or CT scans if MRI is 
contraindicated) as indicated on the Study Calendar.  
A radiographic spleen response is defined per IWG-MRT criteria26 as a ≥ 35% volume 
reduction in the spleen (by MRI or CT), regardless of what is reported with physical 
examination. See Appendix 5 for details. 
 
Efficacy Based on Patient Reported Outcomes 
Subjects will complete the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-
SAF, see Appendix 7) at baseline and at each subsequent clinic visit (C1D8, C1D15, D1 of 
each subsequent cycle, EOT). Their Total Symptoms Score (TSS) will be calculated at each 
time point. 
A symptoms response is defined per IWG-MRT criteria26 as a ≥ 50% reduction in the MPN-
SAF TSS. See Appendix 5 for details. 
 
Overall Response 
Overall response criteria are based on the 2013 International Working Group-
Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria for 
myelofibrosis (listed in Appendix 5).26  
The overall response rate (CR, PR, CI) from after six cycles of treatment is defined in 
Appendix 5. 
 
Overall Survival  
Patients will be followed for 24 months from the initiation of study treatment. Overall 
survival will be assessed from initiation of study therapy to 24 months or death from any 
cause. Patients will be censored at 24 months.  
10.3 
Stopping Rules 
 
Original Design  
Up to 24 patients will be treated with the maximum tolerated dose of selinexor. Subjects will 
be enrolled in treatment cohorts of 8 subjects each and there will be a safety evaluation after 
each cohort has completed 1 cycle of treatment. Initially, 8 subjects will be enrolled in 
Cohort 1 and treated at a starting dose of 80 mg once weekly. The starting dose will be 
reduced by 1 dose level for all future patients after more than 2 patients in Cohort 1 require 
dose reduction for excess toxicity defined in section 7. Another set of up to 8 patients will be 
enrolled in Cohort 2. If more than 2 of 8 subjects in Cohort 2 (alone) require dose reduction 
for excess toxicity, then the starting dose will be reduced by 1 dose level in Cohort 3. 
Regardless of dose reduction, no cohort will ever contain more than 8 patients. The study 
will be discontinued if the starting dose for treatment cohorts is reduced more than 2 dose 
levels. Transition from dose level 1a to dose level -1 will not be considered a dose reduction. 
 
 


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Version 7 Update 
After accrual of 12 patients, 7 patients required dose reduction to 40 mg once weekly. The 
decision was made to accrue the remaining patients at the lowest starting dose of 40 mg once 
weekly. Stopping rules do not apply after protocol version 7. 
11 
STATISTICAL CONSIDERATIONS 
11.1 
Statistical hypothesis 
We hypothesize that treatment with selinexor will produce a clinically meaningful effect on 
the radiographic spleen response rate after six cycles of treatment. 
11.2 
Sample size determination 
Response is defined as a 35% or greater reduction in spleen volume from baseline to after 6 
cycles of treatment. A sample size of 18 evaluable subjects will provide 83% power at one-
sided alpha = 0.05 to reject a response rate of 15% (the null hypothesis) using a one sample 
exact test for a binomial proportion provided the true response rate is 42%. The null 
hypothesis will be rejected if 6 or more out of 18 subjects respond. Patient who discontinued 
treatment and failed to receive 6 cycles of treatment would be considered as non-responders.  
The planned sample size is up to 24 to allow for up to a 25% dropout rate.   
The alternative hypothesis is based on the known radiographic spleen response rate of 
ruxolitinib in MF patients and would indicate comparable efficacy.17,18 The radiographic 
spleen response rate of the standard therapy for patients who fail or can’t tolerate ruxolitinib 
is unknown, and 15% was chosen as a response rate below the minimum clinically 
meaningful response rate. 
11.3 
Statistical Analysis of Dose de-escalation 
 Original Design 
 
Study was originally designed to enroll in treatment cohorts of 8 subjects each with a planned 
safety evaluation after each cohort has completed at least 3 cycles of treatment. Initially, up 
to 8 subjects would be enrolled in Cohort 1 and treated at a starting dose of 80 mg once 
weekly. The starting dose will be reduced by 1 dose level for all future patients after more 
than 2 patients in cohort 1 required dose reduction for excess toxicity as defined in section 7. 
Another set of up to 8 patients will be enrolled in Cohort 2. If more than 2 of 8 subjects in 
cohort 2 (alone) required dose reduction for excess toxicity, then the starting dose would be 
reduced by 1 dose level in Cohort 3.  
 
To date of protocol version 7, 12 patients were dosed with selinexor in this study. The 
starting dose of selinexor was 80 mg weekly in the first six patients.  3 out 6 patients required 
dose reduction due to grade 2 weight loss after at least 1 cycle of treatment. The starting dose 
of selinexor was decreased to 60 mg weekly for subsequent patients. Additional six patients 
were enrolled at starting dose of 60 mg weekly. Of all the 12 patients, 7 patients required 


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dose reduction to 40 mg weekly. The starting dose of selinexor will be decreased to 40 mg 
weekly for the remaining 12 patients. 
 Dose Reduction 
After the initial enrollment of 6 patients, 2 patients required dose reduction by at least 1 dose 
level (60 mg). As per the protocol, at that time all subsequent patients, including the 
remaining 2 patients in cohort 1, were started at 60 mg weekly.   
11.3.2.1 
Version 7 Update 
After enrollment of 12 patients, 7 patients required dose reduction to 40 mg weekly. The 
decision was made to enroll the remaining 12 patients at the starting dose of 40 mg weekly.  
11.4 
Population for analyses 
 
Evaluable for toxicity 
The safety population includes all enrolled patients who received at least 1 dose of the study 
drug. 
 
Evaluable for efficacy 
The intent-to-treat population evaluable for efficacy includes all enrolled patients who 
received at least 1 dose of study medication.  
11.5 
Statistical Analyses 
 
Primary endpoint 
The primary endpoint is defined as the proportion of subjects with ≥ 35% reduction in spleen 
volume as measured by MRI or CT abdomen from baseline to after six cycles of treatment.  
A one sample test of binomial proportions will be performed at the one sided 0.05 
significance level to test this hypothesis. The null hypothesis will be a response rate of 15% 
or less. Counts, proportions and 95% exact binomial confidence intervals (Clopper-Pearson) 
will be reported for each response category.  
 
Secondary endpoints 
Safety and tolerability 
Adverse events, serious adverse events 
AEs will be coded using the MedDRA dictionary and displayed in tables and listings using 
System/Organ/Class (SOC) and Preferred Term. AEs will be summarized by patient incidence 
rates. In all tabulations, a patient may contribute only once to the count for a given AE preferred 
term. The number and percentage of patients AEs will be summarized along with the number 
and percentage of AEs assessed by the Investigator as at least possibly related to treatment. 
The number and percentage of patients with any Grade ≥ 3 AEs will be tabulated in the same 
manner. In the event a patient experiences repeated episodes of the same AE, the event with 
the highest severity and/or strongest causal relationship to study treatment will be used for 
purposes of tabulations. Serious AEs (SAEs) will also be tabulated.  


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All AEs will be listed in patient data listings. Separate by-patient listings will be provided for 
the following: patient deaths, SAEs, and AEs leading to withdrawal. 
No formal hypothesis-testing analysis of AE incidence rates will be performed.  
Laboratory Data  
The actual value and change from baseline for each on-study evaluation will be summarized 
for each clinical laboratory parameter, including hematology and clinical chemistry, by arm, 
and for all study patients combined. In the event of repeat values, the last non-missing value 
per study day/time will be used.  
Severity of select clinical lab measures will be determined using CTCAE criteria (i.e., those 
measures that have a corresponding CTCAE grade classification). Labs with CTCAE Grades 
≥ 3 will be presented in a data listing. Shift tables that present changes from baseline to worst 
on-study values relative to CTCAE classification ranges will be produced.  
Vital signs and physical examinations  
The actual value and change from baseline to each on-study evaluation will be summarized 
for vital signs for all study patients combined. By-patient listings of vital sign measurements 
will be presented in data listings.  
Physical examination results at screening will be summarized; all other abnormal physical 
examination data will be recorded. All examination findings will be presented in a data 
listing. 
Additional Efficacy Analysis 
Change and percentage change in radiographic spleen volume, as well as radiographic spleen 
response rates, will be summarized using descriptive statistics. The mean, range, standard 
deviation and 95% confidence interval will be reported for change and percent change in 
spleen volume.  
The proportion of patients with ≥ 50% reduction of total symptoms score will be summarized 
by observed proportion and exact 95% binomial confidence interval.  
The number and proportion of patients with responses per the IWG-MRT criteria will be 
tabulated and an exact 95% binomial confidence interval for response will be calculated. 
Overall survival from initiation of therapy to 24 months will be estimated using Kaplan-
Meier methods and associated 95% confidence intervals.  
 
Exploratory endpoints 
A statistical plan will be determined for exploratory endpoints prior to the initiation of the 
statistical evaluation.  
12 
REGISTRATION GUIDELINES 
Study related screening procedures can only begin once the patient has signed a consent form.  
Patients must meet all of the eligibility requirements listed in Section 5 prior to registration.  


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Patients must be registered before receiving any study treatment and must begin treatment as 
soon as logistically possible after registration.  
 
To register eligible patients on study, complete a Clinical Trials Office Patient Registration Form and 
submit to CTORegistrations@hci.utah.edu or multisiteregistrations@hci.utah.edu. 
 
13 
DATA SUBMISSION SCHEDULE 
The Case Report Forms (CRFs) are a set of (electronic or paper) forms for each patient that provides 
a record of the data generated according to the protocol. CRFs should be created prior to the study 
being initiated and updated (if applicable) when amendments to the protocol are IRB approved. 
These forms will be completed on an on-going basis during the study. The medical records will be 
source of verification of the data. During the study, the CRFs will be monitored for completeness, 
accuracy, legibility and attention to detail by a member of the Research Compliance Office. The 
CRFs will be completed by the Investigator or a member of the study team as listed on the 
Delegation of Duties Log. The data will be reviewed no less than annually by the Data and Safety 
Monitoring Committee. The Investigator will allow the Data and Safety Monitoring Committee or 
Research Compliance Office personnel access to the patient source documents, clinical supplies 
dispensing and storage area, and study documentation for the above-mentioned purpose. The 
Investigator further agrees to assist the site visitors in their activities. 
Data capture should be restricted to endpoints and relevant patient information required for 
planned manuscripts. 
14 
CORRELATIVE STUDIES  
 
Bone Marrow  
Bone marrow aspirates (5 mL) will be collected at the time points indicated on the Schedule 
of Events of for CD34 selection and testing.  
Bone marrow aspirates and biopsies will be collected at the time points indicated on the 
Schedule of Events for local and central pathology review.  
Instructions for processing and shipping will be detailed in the lab manual. 
 
Blood  
Peripheral blood (20 mL) will be collected at the time points indicated on the Schedule of 
Events for pharmacodynamics studies.  
Peripheral blood (34 mL) will be collected at the time points indicated on the Schedule of 
Events for analysis that may include but are not limited to plasma proteins and cytokines as 
well as for evaluation of changes in mutant allele burden of JAK2, MPL, and CALR RNA.  
Peripheral blood will be collected at the time points indicated on the Schedule of Events for 
local and central pathology review.  
 


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Instructions for processing and shipping will be detailed in the lab manual. 
15 
ETHICAL AND REGULATORY CONSIDERATIONS 
15.1 
Informed consent  
Informed consent will be obtained from all research participants prior to performing any 
study procedures using the most recent IRB-approved version.  
15.2 
Human Subjects Protections 
 
Participation of Children 
Patients must be at least 18 years of age to participate. 
 
Participation of Subjects Unable To Give Consent 
Patients must be able to provide informed consent and willing to sign an approved consent 
form that conforms to federal and institutional guidelines. 
15.3 
Institutional Review 
This study will be approved by the Institutional Review Board of the University of Utah. 
15.4 
Data and Safety Monitoring Plan 
A Data and Safety Monitoring Committee (DSMC) is established at Huntsman Cancer 
Institute (HCI) to ensure the well-being of patients enrolled on Investigator Initiated Trials 
that do not have an outside monitoring review. The roles and responsibilities of the DSMC 
are set forth in the NCI-approved Data and Safety Monitoring (DSM) plan. The activities of 
the committee include reviewing adverse events (including SAEs), deviations, important 
medical events, significant revisions or amendments to the protocol, and approving 
cohort/dose escalations. If the DSMC and/or the PI have concerns about unexpected safety 
issues, the study will be stopped and will not be resumed until the issues are resolved. The 
DSMC also reviews and approves audit reports generated by the Research Compliance 
Office. 
This is a Phase II, multisite study classified as high risk per the NCI-approved DSM plan.  
Each high-risk study may be assigned a physician member of the DSMC as medical monitor, 
or in rare cases, an external medical monitor. The medical monitor will be notified of all 
serious adverse events (SAEs). Specific notifications will also be issued when a dose-limiting 
toxicity is encountered and when the MTD dose is defined. Approval by the medical monitor 
is required for all dose escalations. All serious adverse events (SAEs) occurring in patients 
treated at HCI or its affiliates will also be reviewed by the full DSMC monthly. The full 
committee will also review all toxicities for patients on treatment and within 30 days of their 
last treatment on a quarterly basis.  
Each high-risk study will be assigned a dedicated research compliance officer who will 
monitor the trial. High-risk trials will be monitored by RCO personnel after the first patient is 
enrolled and every three months thereafter during active enrollment. The RCO monitor will 


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review the study status and summarize enrollment, toxicities, SAEs, dose escalation, 
statistical endpoints (e.g., stopping rules), deviations, etc. for the full DSMC membership at 
the regularly scheduled meetings. Amendments that increase risk, change dosing, or impact 
study objectives will be reviewed by the DSMC and approved by the PRMC and IRB. High-
risk trials will be formally reviewed by the DSMC after the first patient is enrolled and then 
quarterly thereafter.  
An initial audit of high-risk studies will be conducted by the RCO approximately one year 
after enrollment begins and annually thereafter. Audits of high-risk studies may be conducted 
more frequently as requested by the DSMC, IRB, PRMC, RCO management, or the PI. 
15.5 
Adverse Events and Serious Adverse Events  
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for AE and SAE reporting.  
 
Adverse Events (AEs) 
An adverse event is the appearance or worsening of any undesirable sign, symptom, or 
medical condition occurring after starting the study drug even if the event is not considered 
to be related to study drug. For the purposes of this study, the terms toxicity and adverse 
event are used interchangeably. Medical conditions/diseases present before starting study 
drug are only considered adverse events if they worsen after starting study drug. Abnormal 
laboratory values or test results constitute adverse events only if they induce clinical signs or 
symptoms, are considered clinically significant, or require therapy. 
Collection of adverse events will begin after the subject’s first dose and end 30 days after the 
last dose of study drug or until a new cancer treatment is initiated, whichever happens 
soonest.  
Information about all adverse events, whether volunteered by the subject, discovered by 
investigator questioning, or detected through physical examination, laboratory test or other 
means, will be collected and recorded and followed as appropriate. 
The occurrence of adverse events should be sought by non-directive questioning of the 
patient at each visit or phone contact during the study. Adverse events also may be detected 
when they are volunteered by the patient during or between visits or through physical 
examination, laboratory test, or other assessments. As far as possible, each adverse event 
should be evaluated to determine: 
1. The severity grade based on CTCAE v.5.0 (grade 1-5) 
2. Its relationship to the study drug(s) (definite, probable, possible, unlikely, not related) 
3. Its duration (start and end dates or if continuing at final exam) 
4. Action taken (no action taken; study drug dosage adjusted/temporarily interrupted; 
study drug permanently discontinued due to this adverse event; concomitant 
medication taken; non-drug therapy given; hospitalization/prolonged hospitalization) 
5. Whether it constitutes an SAE 
All adverse events will be treated appropriately. Such treatment may include changes in 
study drug treatment as listed in the dose modification section of this protocol (see section 8 


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for guidance). Once an adverse event is detected, it should be followed until its resolution, 
and assessment should be made at each visit (or more frequently, if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat it, and the outcome. 
Information about common side effects already known about selinexor are described in the 
Drug Information (Section 3.1) and in the investigator brochure (Selinexor IB v.11). This 
information will be included in the patient informed consent and will be discussed with the 
patient during the study as needed. 
All adverse events will be immediately recorded in the patient research chart.  
 
Adverse Events of Special Interest (AESI) 
AESIs for selinexor include cataracts and acute cerebellar syndrome. All cases of cerebellar 
toxicity, Grade 3 or higher must be reported as described below in a manner similar to SAEs 
(section 15.6). 
All cases of Grade 3 or higher cerebellar toxicities occurring in patients enrolled in the study 
from the informed consent signature and up to 30 days after the last drug administration, or 
after if related to study drug, must be immediately reported as SAE (even if not meeting the 
definition of a SAE) to the drug supplier, within 24 hours of first knowledge of the event, 
following reporting rules for SAE in section 15.6).  
 
Reporting of Cataracts  
The drug supplier is closely monitoring the occurrence of cataracts during treatment with 
selinexor as adverse events of special interest. Optional ophthalmic examinations are planned 
on regular basis to identify cataracts or worsening of existing cataracts. Any cataracts or 
worsening of existing cataracts has to be reported as an AE irrespectively of grade. 
 
Serious Adverse Event (SAE) 
A serious adverse event is defined as any untoward event that is: 
• Fatal; 
• Life-threatening; 
• Results in persistent or significant disability/incapacity; 
• Medically significant; 
• Causes a congenital abnormality or birth defect; 
• Requires or prolongs inpatient hospitalization. 
 
Investigator judgment must be used to assess an event as medically significant. The event 
may not be life-threatening or cause disability but may jeopardize the subject and require 
intervention to prevent the other SAE outcomes. 
 
The following situations should not be reported as an SAE: 


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• Hospital admission not associated with a precipitating AE such as: 
o Treatment for a preexisting condition not associated with a new AE or the 
worsening of a preexisting condition; 
o Admission for social or administrative reasons; 
o Optional admission or elective surgery; 
o Observation; 
o Preplanned treatments or surgical procedures as noted at baseline; 
o Admission for the administration of blood products. 
15.6 
SAE Reporting Requirements 
•  
All serious adverse events should be reported as soon as possible but no later than one 
business day after the Investigator becomes aware. All SAEs must be reported via the HCI 
CTMS (OnCore) and submitted to HCI-RCO@utah.edu and Karyopharm. The HCI Clinical 
Site Monitor will in turn, submit the report to the Medical Monitor. The RCO will summarize 
and present all reported SAEs according to the Data and Safety Monitoring Plan at the 
monthly DSMC meeting. 
At a minimum, initial SAE reports must include a description of the event, assessment of 
event causality, event grade, and the expectedness of the event. Although the Investigator 
may not know all the information at the time of the event, the available information should 
be reported. An SAE follow-up may be submitted at a later date once more information is 
known. It is required that follow-up reports be submitted until the SAE is resolved. 
Follow-Up Information 
It is recommended that follow-up reports be submitted as new information becomes 
available, however, a follow-up report should be submitted within 3 days of knowledge of 
event resolution. Follow-up information will be added to the SAE in OnCore and submitted 
to the DSMC via RCO. 
 
FDA Notifications 
Per 21 CRF 312.32 adverse events and serious adverse events will be reported on a 
MedWatch 3500A form to the FDA. Reportable events will be reported by the RCO 
according to the following guidelines:  
MedWatch 3500A Reporting Guidelines  
In addition to completing appropriate patient demographic (Section A) and suspect 
medication information (Section C & D), the report should include the following information 
within the Event Description (Section B.5) of the MedWatch 3500A form:  
• Protocol number and title description  
• Description of event, severity, treatment, and outcome if known  
• Supportive laboratory results and diagnostics (Section B.6)  


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• Investigator’s assessment of the relationship of the adverse event to each 
investigational product and suspect medication  
• Expectedness of the event (i.e., expected or unexpected event).  
FDA Reporting Timelines:  
• 7 Calendar Day Report:  
Any event that is fatal or life-threatening, unexpected, and definitely, probably or 
possibly related to study medication will be reported to the FDA by telephone or fax 
within seven calendar days of first learning of the event.  
• 15 Calendar Day Report:  
Any event that is serious, unexpected, and definitely, probably or possibly related to 
study medication will be reported to the FDA in an IND safety report within 15 
calendar days of first learning of the event.  
In accordance with 21 CFR 312.32, an Analysis of Similar Events should be included 
in the IND Safety Report. All safety reports previously filed by the investigator with 
the IND concerning similar events should be analyzed and the significance of the new 
report in light of the previous, similar reports commented on.  
FDA fax number for IND Safety Reports:  
Fax: 1 (800) FDA 0178 
 
IRB Notification 
The University of Utah IRB requires any unanticipated problems that may increase the risk to 
research participants be promptly reported. All study-therapy related, unexpected adverse 
events whose nature, severity, or frequency is not consistent with either:  
• The unknown or foreseeable risk of adverse events that are described in the protocol 
related-documents, such as the IRB-approved research protocol, applicable 
investigator brochure, the current IRB-approved informed consent document, and/or 
other relevant sources of information, such as product labeling and package inserts; or  
• The expected natural progression of any underlying disease or condition of the 
subject(s) experiencing the adverse event.  
Adverse events meeting this criterion must be promptly reported to the IRB within 10 
business days of awareness. 
 
Drug Manufacturer Notifications 
All SAEs must be reported to Karyopharm Pharmacovigilance within 24 hours of awareness. 
Reports must be emailed or faxed to:  
Pharmacovigilance Department 
Karyopharm Therapeutics Inc. 
Email: pharmacovigilance@karyopharm.com 
Fax: 
+1-617-334-7617  


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Any SAE observed after the 30-day follow-up period should only be reported to Karyopharm 
if the Investigator suspects that the SAE has causal relationship to study treatment 
In addition to reporting SAEs as described above, the PI will report all AEs (including non-
serious events) to Karyopharm Pharmacovigilance twice per year in the form of line-listings. 
Karyopharm will supply the cut-off dates.  The line listings will contain the following 
information: study ID, unique subject ID, adverse event term, serious event (yes or no), onset 
date (complete or partial), end date (complete or partial), action taken with selinexor, 
causality to selinexor, event ongoing (yes or no), outcome of AE, severity CTCAE Grade (1-
5), subject dosed with selinexor (yes or no), date of first dose of selinexor, preferred term, 
system organ class (optional). 
For multisite studies the HCI DSMC will notify all participating sites of all unexpected and 
related SAEs via the Research Compliance Office. The RCO will also notify all investigators 
at remote clinical sites participating in a multisite trial of any other safety update, including 
manufacturer’s reports and updates to the investigator’s brochure. 
15.7 
Reporting of Pregnancy  
Although pregnancy is not considered an adverse event, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject, including 
the pregnancy of a male subjects’ female partner as an SAE. Pregnancies or lactation that 
occurs during the course of the trial or within 90 days of the last administration of selinexor 
or starting another new anticancer therapy, whichever is earlier, must be reported to the 
DSMC, IRB, FDA, and the drug manufacturer as applicable. All subjects and female partners 
who become pregnant must be followed to the completion/termination of the pregnancy. 
Pregnancy outcomes of spontaneous abortion, missed abortion, fetal death, intrauterine death, 
miscarriage and stillbirth must be reported as serious events.  
15.8 
Overdose 
An overdose is a deliberate or accidental administration of any Karyopharm treatment to a 
study patient, at a dose greater than that which was assigned to that patient per the study 
protocol. If an overdose occurs, Karyopharm should be notified immediately, and the patient 
should be observed closely for AEs. Resulting symptoms should be treated, as appropriate, 
and the incident of overdose and related AEs and/or treatment should be recorded. Overdose 
is to be reported on an FDA 3500A MedWatch form to the DSMC and Karyopharm 
pharmacovigilance regardless of whether or not an AE or SAE has occurred due to the 
overdose. If the overdose is associated with an SAE, the SAE report form must be submitted 
to the DSMC and Karyopharm pharmacovigilance within 24 hours of awareness. If there is 
no AE or SAE, the overdose report must be submitted within 24 hours of awareness. In all 
cases, the IRB and the FDA must be notified as applicable. 
15.9 
Abuse, Misuse, or Medication Error 
Abuse is the persistent or sporadic, intentional excessive use of the study drug which is 
accompanied by harmful physical or psychological effects.  
A medication error is any preventable incident that may cause or lead to inappropriate 
medication use or patient harm while the medication is in the control of the health care 


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professionals or patients. Such incident may be due to health care professional practice, 
product labeling, packaging and preparation, procedures for administration, and systems, 
including prescribing; order communication; and nomenclature; compounding; dispensing; 
distribution; administration; education; monitoring; and use.’ 
All occurrences of abuse, misuse or medication error with Karyopharm drug are to be 
reported on an FDA 3500A MedWatch form to the DSMC and Karyopharm 
pharmacovigilance regardless of whether or not an AE or SAE has occurred due to the abuse, 
misuse or medication error. If the abuse, misuse or medication error is associated with an 
SAE, the SAE report form must be submitted to the DSMC and Karyopharm 
pharmacovigilance within 24 hours of awareness. If there is no AE or SAE, the report must 
be submitted as soon as possible. In all cases, the IRB and the FDA must be notified as 
applicable. 
15.10 
Occupational Exposure 
Occupational exposure is the exposure to a study drug as a result of one’s professional or 
non-professional occupation.   
All occurrences of occupational exposure with Karyopharm drug are to be reported on an 
FDA 3500A MedWatch form to the DSMC and Karyopharm pharmacovigilance regardless 
of whether or not an AE or SAE has occurred due to the occupational exposure. If the 
occupational exposure is associated with an SAE, the SAE report form must be submitted to 
the DSMC and Karyopharm pharmacovigilance within 24 hours of awareness. If there is no 
AE or SAE, the report must be submitted as soon as possible. In all cases, the IRB and the 
FDA must be notified as applicable. 
15.11 
Protocol Amendments 
Any amendments or administrative changes in the research protocol during the period, for 
which the IRB approval has already been given, will not be initiated without submission of 
an amendment for IRB review and approval.   
These requirements for approval will in no way prevent any immediate action from 
being taken by the investigator in the interests of preserving the safety of all subjects 
included in the trial.  
Any amendments to the protocol that significantly affect the safety of subjects, scope of 
the investigation, or the scientific quality of the study are required to submit the 
amendment for FDA review. 
15.12 
Protocol Deviations 
A protocol deviation (or violation) is any departure from the defined procedures and 
treatment plans as outlined in the protocol version submitted and previously approved by the 
IRB. Protocol deviations have the potential to place participants at risk and can also 
undermine the scientific integrity of the study thus jeopardizing the justification for the 
research. Protocol deviations are unplanned and unintentional events.  


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Because some protocol deviations pose no conceivable threat to participant safety or 
scientific integrity, reporting is left to the discretion of the PI within the context of the 
guidelines below. The IRB requires the prompt reporting of protocol deviations which are: 
• 
Exceptions to eligibility criteria. 
• 
Intended to eliminate apparent immediate hazard to a research participant or  
• 
Harmful (caused harm to participants or others, or place them at increased risk of 
harm - including physical, psychological, economic, or social harm), or  
• 
Possible serious or continued noncompliance  
15.13 
FDA Annual Reporting  
An annual progress report will be submitted to the FDA within 60 days of the anniversary of 
the date that the IND went into effect. (21 CFR 312.33).  
15.14 
Clinical Trials Data Bank  
The study will be registered on http://clinicaltrials.gov and the NCI CTRP (Clinical Trials 
Reporting Program) by the Clinical Trials Office. 
15.15 
Record Keeping 
Per 21 CFR 312.57, the Investigator records shall be maintained for a period of 2 years 
following the date a marketing application is approved; or, if no application is filed or the 
application is not approved, until 2 years after the investigation is discontinued and the FDA 
is notified. 
 


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16 
APPENDICES 
16.1 
Appendix 1 - Eastern Cooperative Oncology Group Performance Status 
Criteria (ECOG) & Karnofsky Performance Scale Index (KPS) equivalency 
ECOG Performance Status Scale1 
 
Karnofsky Performance Scale2 
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 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 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. 
1. Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology 
Group. Am J Clin Oncol.1982;5:649-655. 
2. Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, 
ed. Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–205. 


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16.2 
Appendix 2 - Ophthalmic Exam 
An ophthalmic examination by an optometrist or ophthalmologist is optional at screening and 
if clinically indicated during the study (e.g., monitoring of pre-existing cataracts, visual 
disturbances). 
The optional examination is to include the following:  
Prior to dilation:   
• Best corrected visual acuity  
• Slit lamp examination 
• Tonometry 
Following dilation:  
• Fundoscopy 
• Slit lamp examination to document lens clarity  
If a cataract/lens opacity is seen during the examination, the cataract/lens opacity will be 
graded according to a Grade 1-4 system (modified from Optometric Clinical Practice 
Guideline: Care of the Adult Patient with Cataracts: available on the American Optometric 
Association website: www.aoa.org).   
Grading of Cataracts* 
Cataract Type 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Nuclear 
Yellowing and sclerosis 
of the lens nucleus 
Mild 
Moderate 
Pronounced 
Severe 
Cortical 
Measured as aggregate 
percentage of the 
intrapupillary space 
occupied by the opacity 
Obscures 10% 
of intrapupillary 
space 
Obscures 10% -
50% of intra-
pupillary space 
Obscures 50% -
90% of intra-
pupillary space 
Obscures >90% 
of intrapupillary 
space 
Posterior subcapsular 
Measured as the 
aggregate percentage of 
the posterior capsular 
area occupied by the 
opacity 
Obscures 10% 
of the area of 
the posterior 
capsule 
Obscures 30% 
of the area of 
the posterior 
capsule 
Obscures 50% 
of the area of 
the posterior 
capsule 
Obscures >50% 
of the area of the 
posterior capsule 
*Designation of cataract severity that falls between grade levels can be made by addition of a + sign 
(e.g., 1+, 2+). Grading of cataracts is usually done when pupil is dilated. 
 
 
 


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16.3 
Appendix 3 - NCCN Clinical Practice Guidelines in Oncology: Antiemesis 
Available at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf. 
Reproduced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN 
Guidelines®) for Antiemesis V.2.2020. © 2020 National Comprehensive Cancer Network, Inc. All 
rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form 
for any purpose without the express written permission of the NCCN. To view the most recent and 
complete version of the NCCN Guidelines, go online to www.nccn.org. NATIONAL 
COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN 
Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 
 
 


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Available at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf. 
Reproduced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN 
Guidelines®) for Antiemesis V.2.2020. © 2020 National Comprehensive Cancer Network, Inc. All 
rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form 
for any purpose without the express written permission of the NCCN. To view the most recent and 
complete version of the NCCN Guidelines, go online to www.nccn.org. NATIONAL 
COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN 
Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 
 
 


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16.4 
Appendix 4 - NCCN Clinical Practice Guidelines in Oncology: 
Anorexia/Cachexia 
Reproduced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN 
Guidelines®) for Palliative Care V.1.2020. © 2020 National Comprehensive Cancer Network, Inc. 
All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any 
form for any purpose without the express written permission of the NCCN. To view the most recent 
and complete version of the NCCN Guidelines, go online to www.nccn.org. NATIONAL 
COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN 
Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 
 
 


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16.5 
Appendix 5 - International Working Group-Myeloproliferative Neoplasms 
Research and Treatment (IWG-MRT) Criteria for myelofibrosis 
Response 
Categories 
Required Criteria (for All Response Categories, Benefit Must Last for ≥ 12 Weeks 
to Qualify as a Response)  
CR 
Bone marrow1: Age-adjusted normocellularity; <5% blasts; ≤Grade 1 MF2 and 
Peripheral blood: Hemoglobin ≥ 100 g/L and < UNL; neutrophil count ≥ 1 × 109/L and 
< UNL; 
Platelet count ≥ 100 × 109/L and < UNL; < 2% immature myeloid cells3 and 
Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence 
of EMH 
PR 
Peripheral blood: Hemoglobin ≥ 100 g/L and < UNL; neutrophil count ≥ 1 × 109/L and 
< UNL; platelet count ≥ 100 × 109/L and < UNL; < 2% immature myeloid cells3 and   
Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence 
of EMH or  
Bone marrow:1 Age-adjusted normocellularity; < 5% blasts; ≤ Grade 1 MF2; and 
peripheral blood: hemoglobin ≥ 85 g/L but < 100 g/L and < UNL; neutrophil count ≥ 1 
× 109/L and < UNL; platelet count ≥ 50 × 109/L but < 100 × 109/L and < UNL; < 2% 
immature myeloid cells3 and  
Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence 
of EMH  
CI 
The achievement of anemia, spleen or symptoms response without progressive disease 
or increase in severity of anemia, thrombocytopenia, or neutropenia4 
Anemia 
Response 
Transfusion-independent patients: a ≥ 20 g/L increase in hemoglobin level5 
Transfusion-dependent patients: becoming transfusion-independent6 
Spleen 
Response7 
A baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not 
palpable8 or  
A baseline splenomegaly that is palpable at > 10 cm, below the LCM, decreases by ≥ 
50%8 
A baseline splenomegaly that is palpable at < 5 cm, below the LCM, is not eligible for 
spleen response  
A spleen response requires confirmation by MRI or CT showing ≥ 35% spleen volume 
reduction  
Symptoms 
response 
A ≥ 50% reduction in the MPN-SAF TSS9 
Progressive 
disease10 
Appearance of a new splenomegaly that is palpable at least 5 cm below the LCM or  
A ≥ 100% increase in palpable distance, below LCM, for baseline splenomegaly of 5-
10 cm or  
A 50% increase in palpable distance, below LCM, for baseline splenomegaly of > 10 
cm or  
Leukemic transformation confirmed by a bone marrow blast count of ≥ 20% or A 
peripheral blood blast content of ≥ 20% associated with an absolute blast count of ≥ 1 
× 109/L that lasts for at least 2 weeks 
Stable 
Disease 
Belonging to none of the above-listed response categories 
Relapse 
No longer meeting criteria for at least CI after achieving CR, PR, or CI, or 
Loss of anemia response persisting for at least 1 month or  
Loss of spleen response persisting for at least 1 month  


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Page 67 of 72 
Abbreviations: LCM = left costal margin; MF = myelofibrosis; MPN-SAF TSS = Myeloproliferative 
Neoplasm Symptom Assessment Form Total Symptom Score; MRI = magnetic resonance imaging; 
PR = partial response; PRBC = packed red blood cell; UNL = upper normal limit. 
1. Baseline and post-treatment bone marrow slides are to be interpreted at 1 sitting by a central 
review process. Cytogenetic and molecular responses are not required for CR assignment. 
2. Grading of MF is according to the European classification.a It is underscored that the consensus 
definition of a CR bone marrow is to be used only in those patients in which all other criteria are 
met, including resolution of leukoerythroblastosis. It should also be noted that it was a 
particularly difficult task for the working group to reach a consensus regarding what represents a 
complete histologic remission. 
3 
Immature myeloid cells constitute blasts + promyelocytes + myelocytes + metamyelocytes + 
nucleated red blood cells. In splenectomized patients, < 5% immature myeloid cells is allowed. 
4. See above for definitions of anemia response, spleen response, and progressive disease. Increase 
in severity of anemia constitutes the occurrence of new transfusion dependency or a ≥ 20 g/L 
decrease in hemoglobin level from pretreatment baseline that lasts for at least 12 weeks. Increase 
in severity of thrombocytopenia or neutropenia is defined as a 2-grade decline, from pretreatment 
baseline, in platelet count or absolute neutrophil count, according to the CTCAE version 5.0. In 
addition, assignment to CI requires a minimum platelet count of ≥ 25,000 × 109/L and absolute 
neutrophil count of ≥ 0.5 × 109/L. 
5. Applicable only to patients with baseline hemoglobin of < 100 g/L. In patients not meeting the 
strict criteria for transfusion dependency at the time of study enrollment (see as follows), but have 
received transfusions within the previous month, the pretransfusion hemoglobin level should be 
used as the baseline. 
6. Transfusion dependency before study enrollment is defined as transfusions of at least 6 units of 
PRBCs, in the 12 weeks prior to study enrollment, for a hemoglobin level of < 85 g/L, in the 
absence of bleeding or treatment-induced anemia. In addition, the most recent transfusion episode 
must have occurred in the 28 days prior to study enrollment. Response in transfusion-dependent 
patients requires absence of any PRBC transfusions during any consecutive "rolling" 12-week 
interval during the treatment phase, capped by a hemoglobin level of ≥ 85 g/L. 
7. In splenectomized patients, palpable hepatomegaly is substituted with the same measurement 
strategy. 
8. Spleen or liver responses must be confirmed by imaging studies where a ≥ 35% reduction in 
spleen volume, as assessed by MRI or CT, is required. Furthermore, a ≥ 35% volume reduction in 
the spleen or liver, by MRI or CT, constitutes a response regardless of what is reported with 
physical examination. 
9. Symptoms are evaluated by the MPN-SAF TSS. The MPN-SAF TSS is assessed by the patients 
themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, 
bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it 
can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the 
summation of all the individual scores (0-100 scale). Symptoms response requires ≥ 50% 
reduction in the MPN-SAF TSS. 
10. Progressive disease assignment for splenomegaly requires confirmation by MRI or CT showing a 
≥ 25% increase in spleen volume from baseline. Baseline values for both physical examination 
and imaging studies refer to pretreatment baseline and not to post-treatment measurement. 
a. 
Thiele J, Kvasnicka HM, Facchetti F, van der Walt J, Orazi A. European consensus on grading bone 
marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128-32. 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Page 68 of 72 
16.6 
Appendix 6 - Screening Symptoms Form 
Patient Initials: ________ 
Patient Study ID: ____________________ 
Please fill out all questions reflecting how these symptoms affected you at their worst 
moment over the past 7 days. Please give the answer that best reflects your opinion. 
Symptom  
1 to 10 (0 if absent) ranking  
1 is most favorable and 10 least favorable 
1. During the past 7 days, how severe 
were your worst night sweats (or 
feeling hot or flushed) due to MF? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
2. During the past 7 days, how severe 
was your worst itchiness due to MF? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
3. During the past 7 days, how severe 
was your worst abdominal discomfort 
(feel uncomfortable, pressure or 
bloating) due to MF? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
4. During the past 7 days, how severe 
was your worst pain under the ribs on 
the left side due to MF? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
5. During the past 7 days, how severe 
was your worst fullness (early satiety) 
you had after beginning to eat, due to 
MF? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
6. During the past 7 days, how severe 
was your worst bone or muscle pain 
due to MF (not joint or arthritis pain)? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
7. During the past 7 days, what was 
the worst degree of inactivity (work 
or social activities) you had due to 
MF (not joint or arthritis pain)? 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
For Investigators/site staff: 
Please confirm the criterion based on assessment of subject’s active symptoms of 
myelofibrosis.  
Criterion Review 
Confirmation 
A symptoms score of at least 5 on at least 1 of the symptoms  
☐Yes      ☐ No 
A symptoms score of 3 or greater on at least 2 of the symptoms 
☐Yes      ☐ No 
Investigator signature: _______________________ 
Date: ___________ 
 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Page 69 of 72 
16.7 
Appendix 7 - Myeloproliferative Neoplasms Symptom Assessment Form- Total 
Symptom Score (MPN-SAF TSS) Form 
Patient Initials: ______________________ 
Study Time Point (cycle/day): __________ 
Patient Study ID: ____________________ 
Date: __________
Please fill out all questions by circling the one number that best describes your symptoms at their 
worst moment. Please give the answer that best reflects your opinion. 
Symptom  
1 to 10 (0 if absent) ranking  
1 is most favorable and 10 least favorable 
Please rate your fatigue (weariness, 
tiredness) by circling the one number 
that best describes your WORST 
level of fatigue during past 24 hours 
(No Fatigue)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
 
 
Circle the one number that describes how, during the PAST WEEK how much  
difficulty you have had with each of the following symptoms 
Filling up quickly when you eat 
(Early satiety) 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Abdominal discomfort 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Inactivity 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Problems with concentration 
(compared to prior to my MPD) 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Numbness/ Tingling  
(in my hands and feet) 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Night sweats 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Itching (pruritus) 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Bone pain  
(diffuse, not joint pain or arthritis) 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
Fever (>100 F) 
     (Absent)  0  1  2  3  4  5  6  7  8  9  10  (Daily) 
Unintentional weight loss  
(last 6 months) 
(Absent)  0  1  2  3  4  5  6  7  8  9  10  (Worst Imaginable) 
 
What is your Overall  
Quality of Life?  
(As good as it can be)  0  1  2  3  4  5  6  7  8  9  10  (As bad as it can be) 
Patient signature: _______________________ 
Date: ___________ 
 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Page 70 of 72 
16.8 
Appendix 8 – Primary Myelofibrosis Dynamic International Prognostic 
Scoring System (DIPSS) 
 
The DIPSS score assigns points for the following five variables: 
  
Prognostic Variable 
Point per Factor 
Age > 65 years 
1 
Hemoglobin < 10 g/dL 
2 
White Blood Cells > 25 K/uL 
1 
Circulating Blasts ≥ 1% 
1 
Constitutional Symptoms* 
1 
 
Total risk score 
Risk category 
Median overall survival  
0 
Low 
not reached 
1 to 2 
Intermediate-1 
14.2 years 
3 to 4 
Intermediate-2 
4 years 
5 to 6 
High 
1.5 years 
 
• *Constitutional symptoms include: 
o Weight loss>10% of the baseline value in the year preceding PMF diagnosis 
o Unexplained fever or excessive sweats persisting for more than one month.  
 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Page 71 of 72 
17 
REFERENCES 
 
 
1. Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol. 2005;23(33):8520–
8530. 
2. Mehta J, Wang H, Iqbal SU, et al. Epidemiology of myeloproliferative neoplasms in the United 
States. Leukemia and Lymphoma. 2014;55(3):595–600 
3. Mesa RA, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant 
impact on patients' overall health and productivity: the MPN Landmark survey. BMC Cancer. 
2016;16:167 
4. Price GL, Davis KL, Karve S, et al. Survival Patterns in United States (US) Medicare Enrollees with 
Non-CML Myeloproliferative Neoplasms (MPN). PLoS One. 2014;9(3):e90299 
5. Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson 
B, Ferarri ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Harrison CN, Radia D, Mesa RA. 
The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective 
validation and reliability trial in 402 patients. Blood. 2011;118(2):401–8 
6. Emanuel RM, Dueck AC, Geyer HL, et al. Myeloproliferative neoplasm (MPN) symptom assessment 
form total symptom Score: Prospective international assessment of an abbreviated symptom burden 
scoring system among patients with MPNs. J Clin Oncol. 2012;30:4098–4103 
7. Mesa RA, Vannuchi AM, Mead A et al. Pacritinib 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–e236 
8. Mesa RA, Kiladjian JJ, Catalano JV. SIMPLIFY-1: A phase III randomized trial of momelotinib 
versus ruxolitinib in Janus Kinase Inhibitor-Naïve patients with myelofibrosis. J Clin Oncol. 
2017;35(34):3844–3850 
9. Mascarenhas J, Hoffman R, Talpaz M. Results of the Persist-2 Phase 3 Study of Pacritinib (PAC) 
Versus Best Available Therapy (BAT), Including Ruxolitinib (RUX), in Patients (pts) with 
Myelofibrosis (MF) and Platelet Counts < 100,000/µl. Blood. 2016;128:LBA-5. 
10. Harrison CN, Vannucchi AM, Platzbecker U et al. Phase 3 randomized trial of momelotinib (MMB) 
versus best available therapy (BAT) in patients with myelofibrosis (MF) previously treated with 
ruxolitinib (RUX). J Clin Oncol. 2017; 35(15_suppl):7001 
11. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, 
Demory JL, Barosi G, Rumi E, Tefferi A. New prognostic scoring system for primary myelofibrosis 
based on a study of the International Working Group for Myelofibrosis Research and Treatment. 
Blood. 2009;113(13):2895–901 
12. Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in 
primary myelofibrosis: a study by the IWG-MRT (International Working Group for 
Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703 
13. Passamonti F, Cervantes F, Vannucchi AM. Dynamic International Prognostic Scoring System 
(DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood. 
2010;116(15):2857 
14. Nangalia J, Green TR. The evolving genomic landscape of myeloproliferative neoplasms. 
Hematology Am Soc Hematol Educ Program. 2014(1):287–96 
15. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative 
myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472 
16. Kiladjian JJ. Current therapies and their indications for the Philadelphia-negative myeloproliferative 
neoplasms. Am Soc Clin Oncol Educ Book. 2015:e389–96 
 
 


Short Title: Selinexor in myelofibrosis refractory or intolerant to JAK 1/2 inhibitors (ESSENTIAL) 
Version Date: 16MAR2023 
Page 72 of 72 
 
17. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available 
Therapy for Myelofibrosis. N Engl J Med 2012;366(9):787–798 
18. Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for 
Myelofibrosis. N Engl J Med 2012; 366(9):799–807 
19. Deininger M, Radich J, Burn TC, et al. The effect of long-term ruxolitinib treatment on 
JAK2p.V617F allele burden in patients with myelofibrosis. Blood. 2015;126(13):1551–1554 
20. Rondelli D, Goldberg JD, Isola L, et al. MPD-RC 101 prospective study of reduced-intensity 
allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 
2014;124(7):1183–91 
21. Tan DSP, Bedard PL, Kuruvilla J, et al. Promising SINEs for Embargoing Nuclear–Cytoplasmic 
Export as an Anticancer Strategy. Cancer Discovy. 2014;4(5);527–37 
22. Khorashad JS, Eiring AM, Mason CC, et al. shRNA library screening identifies nucleocytoplasmic 
transport as a mediator of BCR-ABL1 kinase-independent resistance. Blood. 2015;125(11):1772–81) 
23. Yan D, Pomicter AD, Tantravahi SK, et al. Nuclear-Cytoplasmic transport is a therapeutic target in 
myelofibrosis. Clin Cancer Res. 2019;25(7):2323-2335. 

ICF_001.pdf: 
Srinivas Tantravahi, MBBS, MRCP 
 
Page 1 of 14 
IRB# 114354 IIT Karyopharm ESSENTIAL 
Consent Version: 16MAR2023 
Previous Version: 01MAR2022 
 
FOOTER FOR IRB USE ONLY 
Version: K1315 
 
 
University of Utah 
Institutional Review Board 
Approved 2/15/2024 
Expires 2/14/2025 
IRB_00114354 
 
 
Consent and Authorization Document 
A Phase II Study to Evaluate the Efficacy and Safety of Selinexor in Patients with Myelofibrosis 
Refractory or Intolerant to JAK1/2 Inhibitors (ESSENTIAL) 
 
You are being asked to take part in a research study. Before you decide whether or not to participate, it 
is important for you to understand why the research is being done and what it will involve. Please take 
time to read the following information carefully and discuss it with friends and relatives if you wish. Ask 
the research doctor or staff if there is anything that is not clear or if you would like more information. 
Take time to decide whether or not to volunteer to take part in this research study. 
 
 
Once you know about the study, you will make a decision about whether to take part. If you decide to 
take part, you’ll be asked to sign this form. Your decision to take part in this study is voluntary which 
means you are free to decide to join this study or not to join this study.   
 
BACKGROUND 
You are being asked to take part in this study because you have a condition called myelofibrosis and other 
drug(s) that you have tried have either not worked well or have caused too many side effects or side 
effects which are too severe. In this study you will be given a drug called selinexor. The main reason for 
the study is to determine the effect that selinexor will have on your disease.  
 
Selinexor (KPT-330) has not been approved by the U.S Food and Drug Administration (FDA), or any other 
agency, so it is being considered “investigational” for use in this study. An investigational drug is a drug 
that is being tested and is not approved for sale in the United States by the U.S. Food and Drug 
Administration (FDA). 
 
The study is being conducted by Dr. Srinivas Tantravahi at Huntsman Cancer Institute of the University of 
Utah. Karyopharm Therapeutics, Inc. is supplying the study drug, selinexor, and funding for this study. 
 
The chest X-ray and MRIs (Magnetic Resonance Imaging) that are to be performed as part of this study 
are considered standard of care and would be done regardless of your participation in this research study.  
If you are unable to have an MRI you will have a CT (Computerized Tomography) scan. CT scans are not 
considered standard of care and would be done for research purposes.  
 
STUDY PROCEDURES 
If you decide you would like to take part in the study and you sign this informed consent form, you will 
have screening tests and procedures done to make sure you are eligible to participate.  
 
Screening Period 
• 
Medical history will be collected as well as details about what medications, vitamins, and 
supplements you are currently taking. 
• 
You will have a physical exam and a measure of your vital signs, including height, weight, body 
surface area (BSA), and body mass index (BMI). 


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IRB_00114354 
 
 
• 
You will have an evaluation of your ability to perform everyday activities (performance status). 
• 
You will answer questionnaires about how you are feeling and your disease. 
• 
You may have an optional eye exam. 
• 
You will have a MRI to assess your current disease, unless you are unable to have an MRI, then 
you will have a CT scan. You will also have a chest X-ray.  
• 
You will have an ECG (Electrocardiogram) to check your heart function.  
• 
You will have your blood drawn for standard lab testing to ensure you are healthy enough to take 
part. If you are a female with the potential of becoming pregnant, you will have a pregnancy test. 
You will also have tests done to check different components of your cancer and blood, including 
genetics, which will be compared to samples that will be collected later. In addition to your 
standard of care labs, we are going to collect approximately 6 teaspoons for research purposes. 
You will have a bone marrow aspirate and biopsy. These will be checked to help give us 
information about your cancer and its genetic components. A bone marrow aspirate is a test in 
which your skin is numbed, and a needle is inserted into the bone to remove part of the liquid 
bone marrow.  A piece of the bone is also removed (bone marrow biopsy) and tested. 
• 
You will have a nutritional consultation. 
 
Treatment Period 
Once it is decided that you are able to enroll into this study, you will begin study treatment. The study is 
divided up into segments of time called “cycles”. For this study, a cycle will be 28 days. Selinexor will be 
given to you as oral tablets, and should be taken once a week. You will take the tablets either at the clinic 
on visit days, or at home. You will take a 40 mg dose, unless directed otherwise by your doctor and/or 
study team. It should be taken with at least 4 ounces (120 mL) of fluids (water, juice, etc.) at approximately 
the same time each day.  Selinexor tablets should be swallowed whole (not crushed). You may also be 
given medications to help with common known side effects before you take your first dose.    
 
You will come to the clinic on Day 1 of each cycle for your study treatment and Day 15 for lab testing. On 
your first cycle only, you will also come on or around days 8 and 22 for procedures and tests. You will also 
return for Day 15 of each cycle through cycle 6 for lab testing and every 3 months after that unless your 
doctor feels it is necessary for you to return for follow up sooner. Some of the procedures are being done 
as part of your routine cancer care. Some are being done because you are participating in this study. By 
participating in this study, you may be required to spend extra time at each visit. Ask your study team for 
more information about how long each visit may be. You will continue on the study treatment as long as 
you are receiving clinical benefit from the treatment as determined by the study doctor. Treatment will 
be stopped if your disease gets worse, you have intolerable side effects, you decide to stop, or your doctor 
decides it would be in your best interest to stop, or the study is terminated by the study sponsor or drug 
supplier. Your study team will give you more information about your treatment plan.  
 
You will be called 3 days after your first dose of selinexor to ensure that you are feeling okay and to make 
any changes to medications that you were given for possible side effects.  
 
 


Srinivas Tantravahi, MBBS, MRCP 
 
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Study Procedures during the Treatment Period: 
• 
You will have physical exams and measures of your vital signs including weight and body mass 
index (BMI). You will also be asked about any changes in medications that you are taking and 
changes in how you are feeling to check for potential side effects. 
• 
Evaluations of your ability to perform everyday activities (performance status). 
• 
You will also be asked to complete a questionnaire about any symptoms you are having and how 
you have been feeling once a week. This will either be at a clinic visit, or at home if you don’t have 
a clinic visit that week. 
• 
You may have an optional eye exam. 
• 
You will have MRIs, unless you are unable to have an MRI for any reason, then you will have CT 
scans. These will be done at weeks 12 and 24. Unless your disease gets worse before week 24, in 
which case you will have one at the time it gets worse. If you continue to receive clinical benefit 
from the study drug, you will continue on the study and have an MRI or CT scan at months 9, 12, 
and 18. 
• 
If your doctor feels it is necessary, you will have ECGs done.  
• 
You will have blood draws collected for the following reasons. There may be one or more blood 
draws during a clinic visit: 
o 
Standard lab testing for safety. 
o 
To look at the immune system components of your blood as well as genetic components and 
how they have changed since starting treatment. 
o To see how your cancer is responding to the treatment.  
• 
Bone marrow aspirate and biopsy – At 6 months, 18 months, and yearly thereafter until treatment 
discontinuation you will have a bone marrow aspirate and biopsy.  These will be checked to help 
give us information about your cancer and its genetic components and how they may have 
changed since you were on treatment.  
 
End of Treatment 
This visit will take place 5 to 9 days after you go off of study treatment. The following procedures will be 
done:  
• 
You will have physical exams and measures of your vital signs including weight and body mass 
index (BMI). You will also be asked about any changes in medications that you are taking and 
changes in how you are feeling to check for resolution of any side effects you may have 
experienced, and assess for any new ones. 
• 
Evaluations of your ability to perform everyday activities. 
• 
You will also be asked to complete a questionnaire about any symptoms you are having and how 
you have been feeling.  
• 
You may have an optional eye exam. 
• 
You will have an MRI, unless you are unable to have an MRI for any reason, then you will have a 
CT scan unless you had a scan within 6 weeks of this visit.   
• 
You will have an ECG.  
• 
You will have a blood draw (approximately 6 tsp for research) collected for the following reasons: 
o 
Standard lab testing for safety. 


Srinivas Tantravahi, MBBS, MRCP 
 
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IRB# 114354 IIT Karyopharm ESSENTIAL 
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Expires 2/14/2025 
IRB_00114354 
 
 
o 
To look at the immune system components of your blood as well as genetic components and 
how they have changed since starting treatment. 
• 
Bone marrow aspirate and biopsy – At end of treatment, you will have a bone marrow aspirate 
and biopsy. These will be checked to help give us information about your cancer and its genetic 
components and how they may have changed since you were on treatment.  
 
Follow-up 
You will be contacted by phone every 3 months to check on your disease status and to see how you are 
feeling and to see if you have started any new treatments for approximately 24 months. If you have 
recently had a clinic visit this information may be collected from your medical record.  
 
RISKS 
Selinexor 
The side effects listed below are based on the information known to Karyopharm, the drug supplier, 
from previous studies of the study drug and which may or may not be related to the study drug. Not all 
patients have these side effects. It is possible that new side effects of the study drug not described here 
may occur in this study. If these new side effects are determined to be significant and that all patients 
should be informed of them, you will receive this information at that time. If you do not understand 
what any of these side effects mean, please ask the study doctor or study staff to explain these terms to 
you. 
 
Very common side effects (≥ 10%): 
In 100 people receiving selinexor more than 10 people may have: 
• 
Nausea 
• 
Vomiting 
• 
Diarrhea 
• 
Weight loss 
• 
Constipation 
• 
Fatigue and asthenia – loss of energy; weakness 
• 
Decreased appetite 
• 
Dehydration 
• 
Abdominal pain 
• 
Dysgeusia – change in taste 
• 
Shortness of breath 
• 
Cough 
• 
Dizziness 
• 
Fever 
• 
Blurred Vision 
• 
Headache 
• 
Difficulty falling asleep 
• 
Low platelets in the blood (thrombocytopenia), which may increase the risk of bleeding 


Srinivas Tantravahi, MBBS, MRCP 
 
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• 
Decrease in red blood cells (anemia) causing fatigue 
• 
Decrease in white blood cells (leukopenia), which may increase the risk of infection 
• 
Decrease in neutrophils (a specific type of white blood cell that helps fight infections) 
• 
Pneumonia 
• 
Low blood sodium which may increase the risk of seizures 
• 
Low potassium which may cause weakness, muscle cramps and spasms 
• 
Peripheral edema – swelling in extremities due to accumulation of fluid, usually in legs 
• 
High blood sugar which may cause fatigue, increased thirst/hunger, frequent urination, weight 
loss, numbness and tingling in hands/feet 
 
Common side effects (≥ 1-10%):  
In 100 people receiving selinexor about 1 to 10 people may have: 
• 
Rash 
• 
Eye disorders including cataract (new or worsened), dry eye, visual impairment, seeing flashes of 
light 
• 
Night sweats 
• 
Dry mouth 
• 
Stomatitis – a condition that causes painful swelling and sores inside the mouth 
• 
Dyspepsia – indigestion 
• 
Chills 
• 
Hypotension – low blood pressure 
• 
Hypertension 
• 
Tachycardia – fast heart rate 
• 
Nosebleed 
• 
Contusion (bruise due to body injuries such as fall) 
• 
Electrolyte disturbances including: 
o Low phosphate which may cause muscle weakness and fatigue 
o Low magnesium which may cause muscle twitches and cramps 
o Low calcium which may cause numbness and tingling in hands/feet/face, muscle 
stiffness and cramps 
o High potassium which may cause muscle weakness, palpitations or irregular heartbeats 
and chest pain 
• 
Low albumin (which may cause swelling especially of the hands/feet, weakness or exhaustion) 
• 
Peripheral neuropathy – weakness, numbness, and pain from nerve damage, usually in the 
hands and feet 
• 
Decrease in lymphocytes – a specific type of white blood cell that are part of your immune 
system 
• 
Increase of creatinine in the blood due to a reduction of kidney function, often related to 
dehydration 
• 
Elevated liver enzymes including alanine aminotransferase increased, aspartate 
aminotransferase increased, blood alkaline phosphatase increased 


Srinivas Tantravahi, MBBS, MRCP 
 
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• 
Elevated pancreatic enzymes including high amylase and high lipase 
• 
Muscle weakness 
• 
Febrile neutropenia – fever in the absence of a normal white blood cell response that may mean 
you have an infection 
• 
Respiratory tract infection (including upper) 
• 
Urinary tract infection 
• 
Sepsis (including septic shock) – potentially life-threatening complication of an infection 
• 
Pain in joints and muscles 
• 
Malaise (a general feeling of being ill or bodily weakness) 
• 
Muscle spasms 
• 
Gait disturbance 
• 
Hair loss 
• 
Itching 
• 
Depression 
• 
Syncope – fainting 
• 
Cognitive disorder 
• 
Mental status changes including confusion 
 
Uncommon side effects (> 0.1-1%): 
In 1,000 people receiving selinexor about 1 to 10 people may have: 
• 
Tumor lysis syndrome – potentially a life-threatening side effect caused by the rapid breakdown 
of tumor cells and may cause irregular heartbeat, kidney failure or abnormal blood test results 
which included elevated uric acid level, elevated serum potassium and phosphorus levels, and a 
decreased calcium level. 
• 
Enterocolitis infectious (inflammation of digestive tract caused by infection) 
• 
Gastroenteritis (stomach flu) 
• 
Rhinovirus infection (common cold; infection of nose, ear, sinuses; very rarely leading to 
pneumonia or bronchitis) 
 
Rare side effects (> 0.01-0.1%): 
In 10,000 people receiving selinexor about 1 to 10 people may have: 
• 
Acute cerebellar syndrome – symptoms can include a sudden loss of coordination, balance, 
or slurred speech 
 
Serious adverse effects (≥ 3 cases reported as related by the principal investigator): 
• 
Cardiac failure 
• 
General physical health deterioration 
• 
Multiple organ dysfunction syndrome 
• 
Lung infection 
• 
Bacteremia – bacterial infection in the blood 
• 
Bronchitis – infection of tubes that carry air to and from lungs 


Srinivas Tantravahi, MBBS, MRCP 
 
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• 
Decreased ejection fraction – reduction in amount of blood pumped out of heart  
• 
Encephalopathy – brain disease, damage, or malfunction, which can present different 
symptoms that range from mild, such as some memory loss or subtle personality changes, to 
severe, such as dementia, seizures, or coma. 
• 
Delirium – state of acute confusion 
• 
Acute kidney injury 
• 
Pulmonary embolism – pulmonary embolism occurs when a clump of material, most often a 
blood clot, gets wedged into an artery in your lungs. 
• 
Hypoxia – an absence of oxygen supply at tissue level 
 
RADIATION RISKS 
This research study involves exposure to radiation from 4 possible CT scans that will be done if you are 
unable to have an MRI. These scans are being done for the research study and are not considered part 
of your standard care.  The risk from this radiation exposure is considered to be small and comparable to 
other every day risks. This amount does not include any radiation exposures that you may receive from 
other types of tests. 
 
If you are enrolled in this study, the excess 
radiation you will receive is about the same 
as a uniform whole-body dose of: 
The amount of radiation that is considered safe 
for a radiation worker (e.g. doctor, nurse, 
scientist, etc.) to receive in one year: 
1.85 rem 
5 rem 
**A “rem” is a unit of radiation dose. 
 
REPRODUCTIVE RISKS 
It is likely that the study drug may have a potentially harmful effect on the unborn child. If you are a 
sexually active and possibly fertile woman, you will be asked to use 2 medically approved methods of birth 
control (contraception) during the treatment period and for at least 3 months after you finish taking the 
study drug. Examples of medically acceptable birth control include hormonal contraceptives (oral pills, 
patches, vaginal ring, injectables or implants), medically prescribed IUDs, and barrier methods, e.g., male 
and female condoms, cervical cap, diaphragm and sponge. Check with your study doctor about what kind 
of birth control methods to use. Some methods might not be approved for use in this study. If you suspect 
that you have become pregnant during the trial, you must notify the study doctor immediately. You should 
also not breast feed while on this study.  
 
If you are a male that is sexually active with a possibly fertile woman, you must agree to an effective 
barrier method as listed above while taking the study drug and for 3 months after.  
 
If you think that you, or your partner, may be pregnant at any time while on this study, you must inform 
your study doctor immediately. You will be asked to take part in monitoring the outcome of your 
pregnancy and the study doctor will remain in contact with you to determine the conclusion of your 


Srinivas Tantravahi, MBBS, MRCP 
 
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pregnancy. If you are woman and become pregnant while in the study, you will be discontinued from the 
study.  
For more information about risks and side effects, ask your study doctor. 
 
Other Risks and Inconveniences including Genetic Risks 
There are also non-physical risks associated with taking part in this study, such as the risks associated with 
a breach of privacy or confidentiality.  For example, if your identity as a participant in genetic research or 
your identifiable genetic or health information were disclosed to unauthorized persons, there is the 
possible risk of discrimination by employers or insurance providers. The risks of such improper disclosure 
are very small because Huntsman Cancer Institute has adopted strict privacy and confidentiality 
procedures for this research.   
 
Blood draws or IV: Risks associated with drawing blood or putting a needle in your vein might include pain 
from the puncture, bruising, bleeding, infection, or fainting. Every effort will be made to minimize 
discomfort. 
 
Genetic Testing 
In the United States, the Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits 
discrimination in health coverage and employment based on genetic information. GINA, together with 
the Health Insurance Portability and Accountability Act (HIPAA), generally prohibits health insurers or 
health plan administrators from requesting or requiring genetic information of an individual or the 
individual’s family members, or using it for decisions regarding coverage, rates, or preexisting 
conditions. The law also prohibits most employers from using genetic information for hiring, firing, or 
promotion decisions, and for any decisions regarding terms of employment. Utah State Law also offers 
protection against discrimination in health coverage and employment and employment. 
 
The genetic testing that will be done in this trial is called tumor mutation burden analysis. This will only 
be done if you consent to the optional tumor testing at the end of this form. You will not receive the 
results of these tests nor will they be included in your medical records. 
 
UNFORESEEABLE RISKS 
Problems or side effects that are not known could also occur. Most side effects are expected to go away 
after treatment is stopped or interrupted; however, in some cases the side effects may be serious, long-
lasting, permanent or lead eventually to death. You will be given any new information when it becomes 
available that may affect your willingness to start or continue in the study. 
 
BENEFITS 
There may not be any benefit to you from your being in the study. The information gained in this study 
will aid in the understanding of cancer and help in the development of new approaches to its treatment 
in the future. You will not be compensated for participating in this study or as a result of new treatments 
or products developed using information obtained in this study. 
 


Srinivas Tantravahi, MBBS, MRCP 
 
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ALTERNATIVE PROCEDURES 
You do not have to be in this study to get help for the type of cancer you have.  The study doctor will talk 
to you about other things you can do for this type of cancer, including the important risks and benefits.   
Some other things you might do are: 
• 
Use other approved chemotherapy regimens. 
• 
Use other investigational treatments. 
• 
Get supportive care.  
• 
Choose to have no further treatment.  
 
NUMBER OF PARTICIPANTS 
Up to 24 patients are expected to be enrolled in this study from the Huntsman Cancer Institute/University 
of Utah. 
 
PERSON TO CONTACT 
If you have questions, complaints or concerns about this study, you can contact Dr. Srinivas Tantravahi at 
801-585-0255. If you think you may have been injured from being in this study, please call Dr. Tantravahi 
at 801-585-0255. The University Hospital Operator can be reached at this number: 801-581-2121 available 
24-hours a day.  Please ask for the oncologist on call.  
 
Institutional Review Board: Contact the Institutional Review Board (IRB) if you have questions regarding 
your rights as a research participant. Also, contact the IRB if you have questions, complaints or concerns 
which you do not feel you can discuss with the investigator. The University of Utah IRB may be reached 
by phone at (801) 581-3655 or by e-mail at irb@hsc.utah.edu.   
 
Research Participant Advocate:  You may also contact the Research Participant Advocate (RPA) by 
phone at (801) 581-3803 or by email at participant.advocate@hsc.utah.edu.  
 
RESEARCH-RELATED INJURY 
If you are injured from being in this study, medical care is available to you at the University of Utah, as it 
is to all sick or injured people. The University of Utah has not set aside any money to pay the costs for 
such care. The University will work with you to address costs from injuries. Costs would be charged to 
you or your insurance company (if you have insurance), or other third party (if applicable), to the extent 
those parties are responsible for paying for medical care you receive. Since this is a research study, some 
health insurance plans may not pay for the costs. By signing this consent form you are not giving up your 
right to pursue legal action against any parties involved with this research. Karyopharm Therapeutics, 
the drug supplier, is not providing insurance coverage or other compensation to you for this study. 
 
The University of Utah is a part of the government. If you are injured in this study, and want to sue the 
University or the doctors, nurses, students, or other people who work for the University, special laws 
may apply. The Governmental Immunity Act of Utah is a law that controls when a person needs to bring 
a claim against the government, and limits the amount of money a person may recover. See sections 
63G -7-101 to -904 of the Utah Code. 


Srinivas Tantravahi, MBBS, MRCP 
 
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VOLUNTARY PARTICIPATION 
Taking part in this research study is voluntary.  You may decide not to take part or you may leave the study 
at any time.  Refusal to take part or the decision to withdraw from this study will involve no penalty or 
loss of benefits to which you are otherwise entitled.  
 
Tell the study doctor if you are thinking about stopping or decide to stop, as it may be necessary to do 
certain tests in order to ensure your safety.  If you choose not to return for an assessment, we may ask 
for medical records from your current general practitioner in order to continue to monitor your health.   
 
If you decide not to continue in the study at any time, your study doctor will arrange for you to receive 
alternative treatment and any necessary assessments or procedures according to standard of care.   
 
 
RIGHT OF INVESTIGATOR TO WITHDRAW 
Your study doctor may decide to take you off this study at any time without your consent for any of the 
following reasons: 
• 
if your disease becomes worse and is not responding to the study drug, 
• 
if he or she believes it is in your best interest, 
• 
if you do not follow the study rules, 
• 
if you miss study visits and/or procedures, 
• 
if you have serious side effects, 
• 
if you become pregnant, 
• 
you do not later consent to any future changes that may be made in the study plan; or any other 
reason. 
 
There is also the possibility that the investigator, may close the study before your participation is complete 
and without prior warning.  If any of these events were to happen, your study doctor would assist with 
arrangements for your continued care as appropriate. 
 
COSTS AND COMPENSATION TO PARTICIPANTS 
Some of the procedures and treatments you’ll have while you are on the study are considered “standard 
of care” for your type of illness. Even though you will be a part of the study, these types of procedures 
and treatments will be billed to you and/or your insurance company just like regular medical care. Some 
procedures and treatments you’ll have while you are on the study are considered “study related” and are 
not billed to you and your insurance company. You should ask your study coordinator and treating 
physician for details about the specific procedures you or your insurance company will be financially 
responsible for. 
 
Selinexor will be provided to you free of charge in this study by Karyopharm Therapeutics. 
 
 
 


Srinivas Tantravahi, MBBS, MRCP 
 
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NEW INFORMATION 
You will be given any new information about the study drugs that may affect your willingness to start or 
continue in the study as it becomes available. 
 
AUTHORIZATION FOR USE OF YOUR PROTECTED HEALTH INFORMATION  
Signing this document means you allow us, the researchers in this study, and other working with us to use 
some information about your health for this research study. 
 
This is the information we will use and include in our research records: 
• 
Demographic and identifying information like your name, address, telephone number, and email 
address. 
• 
Related medical information about you like family medical history, allergies, current and past 
medications or therapies, information from physical examinations such as blood pressure 
readings, heart rate, temperature, and lab results.  
• 
All tests and procedures that will be done in the study 
 
How we will protect and share your information: 
We will do everything we can to keep your information private, but we cannot guarantee this. The 
research records will be kept in a secured manner and computer records will be password protected. We 
may need to disclose information about you as required by law. 
Study information may be stored with other information in your medical record. Other doctors, nurses, 
and third parties (like insurance companies) may be able to see this information as part of the regular 
treatment, payment, and health care operations of the hospital.  
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. 
 
In order to conduct this study and make sure it is conducted as described in this form, the research records 
may be used and reviewed by others who are working with us on this research: 
• 
Members of the research team and University of Utah Health Sciences Center. 
• 
The University of Utah Institutional Review Board (IRB), who reviews research involving people to 
make sure the study protects your rights. 
• 
Karyopharm Therapeutics, the drug supplier of selinexor, and its authorized agents. 
• 
Government agencies responsible to confirm research accuracy such as the United States Food 
and Drug Administration (FDA), and the National Cancer Institute (NCI) which is a part of the 
National Institute of Health (NIH).  
• 
Governmental agencies in other countries where the study drug may be considered for approval.  
 
If we share your identifying information with groups outside of the University of Utah Health Sciences 
Center, the groups may not be required to follow the same federal privacy laws that we follow. They may 
also share your information again with others not described in this form.  
 


Srinivas Tantravahi, MBBS, MRCP 
 
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What if I Decide Not to Take part After I sign the Consent and Authorization Form? 
You can tell us anytime that you do not want to be in this study and do not want us to use your health 
information. You can also tell us in writing. If you change your mind, we will not be able to collect new 
information about you, and you will be withdrawn from the research study. However, we can continue to 
use information we have already started to use in our research, as needed to maintain the integrity of the 
research. 
 
This authorization does not have an expiration date. 
 
You have a right to information used to make decisions about your health care. However, your information 
from this study will not be available during the study; it will be available after the study is finished. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Srinivas Tantravahi, MBBS, MRCP 
 
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CONSENT 
I have been given adequate time to read and consider the information in this consent form prior to signing 
(or it has been read to me).  All my questions about the study and my participation in it have been 
answered and I will be given a copy of this signed and dated consent form for my records and continued 
reference. 
 
My signature below indicates that I voluntarily agree to take part in this research study.  By signing this 
consent form, I do not release the study doctor or his study staff, the institution or the drug supplier from 
their professional and legal duties. 
 
I authorize the use and disclosure of my health information to the parties listed in the authorization 
section of this consent for the purposes described above.  
 
I agree to take part in this research study and authorize you to use and disclose health information 
about me for this study, as you have explained in this document. 
 
 
________________________ 
Participant’s Name 
 
________________________ 
 
 
 
 
 
____________       __________ 
Participant’s Signature  
   
 
 
 
 
          Date                      Time 
 
________________________ 
Name of Person Obtaining Authorization and Consent 
 
________________________ 
 
 
 
 
 
 ____________       __________ 
Signature of Person Obtaining Authorization and Consent 
 
            Date                     Time 
 
 
LANGUAGE INTERPRETER STATEMENT (if applicable): 
I confirm that I was present as an interpreter for the duration of the consent process for this research 
study.  I confirm that I am qualified/have the necessary skills to provide interpretation between [insert 
target language] _________________ and English. By signing this form, I confirm that I provided a full 
and complete interpretation of the exchange between the research staff member named above and the 
patient named above, to the best of my ability. 
 
                     
Name of Interpreter                                                Employer/Vendor (if applicable) ____________________________ 
 
___________________________________________      ________________ 
____________________________ 
Signature of Interpreter                                                           Date  
                Target Language 
 


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Information requested for federal grant reporting purposes (optional) 
 
Sex/Gender 
 Male 
 Female 
 
Ethnicity 
Do you consider yourself to be Hispanic or Latino? (see definition below) 
 
Hispanic or Latino. A person of Mexican, Puerto Rican, Cuban, South or Central American, or other Spanish 
culture or origin, regardless of race. 
 
Select one: 
 Hispanic or Latino 
 Not Hispanic or Latino 
 
Race 
What race do you consider yourself to be? SELECT ONE OR MORE OF THE FOLLOWING: 
 
 American Indian or Alaska Native. A person having origins in any of the original peoples of North 
America (including, Central or South America) who maintains cultural identification through tribal 
affiliation or community recognition. 
 
 Asian. A person having origins in any of the original peoples of the Far East, Southeast Asia, or the 
Indian subcontinent, including, for example, Cambodia, China, India, Japan, Korea, Malaysia, 
Pakistan, the Philippine Islands, Thailand, and Vietnam. 
 
 Black or African American. A person having origins in any of the black racial groups of Africa. 
 
 Native Hawaiian or other Pacific Islander. A person having origins in any of the original peoples 
of Hawaii, Guam, Samoa, or other Pacific Islands. 
 
 White. A person having origins in any of the original peoples of Europe, the Middle East, or North 
Africa. 
 
 Unknown. 
 
 Check here if you do not wish to provide some or all of the above information.