A Phase II Study of Itacitinib (INCB039110) and Extracorporeal Photopheresis (ECP) for First-Line Treatment in Chronic Graft Versus Host Disease (GVHD)
Phase: PHASE2
Conditions: Chronic Graft-versus-host-disease
Sponsor: University of Utah

Short Title: FLIGHT 
Version Date: 28JAN2022 
Principal Investigator: Catherine Lee, MD 
 
 
 
FLIGHT: A Phase II Study of Itacitinib (INCB039110) and Extracorporeal Photopheresis 
(ECP) for First-Line Treatment in Chronic Graft Versus Host Disease 
IRB # 130090 
Coordinating Center 
Huntsman Cancer Center 
The University of Utah  
2000 Circle of Hope 
Salt Lake City, UT 84112 
Principal Investigator 
Catherine J. Lee, MD 
Huntsman Cancer Institute/University of Utah 
2000 Circle of Hope 
Salt Lake City, UT 84112 
Catherine.Lee@hci.utah.edu 
Statistician(s) 
Kenneth M. Boucher, PhD  
Huntsman Cancer Institute - University of Utah 
2000 Circle of Hope Room 1710 
Email: Ken.Boucher@hci.utah.edu 
Medical Monitor 
Boyu Hu, MD 
Huntsman Cancer Institute 
2000 Circle of Hope 
Salt Lake City, UT 84112 
Boyu.Hu@hci.utah.edu 
Coordinating Center Site 
Contact 
Please contact your assigned Clinical Site Monitor and 
the Clinical Trials Compliance Office 
2000 Circle of Hope 
Salt Lake City, UT 84112 
compliance@hci.utah.edu  
Drug Manufacturer  
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Drug Manufacturer Protocol 
ID 
IIR - I-39110-17-04 
Investigational agent(s) 
INCB039110 Itacitinib 
Commercial treatment 
Extracorporeal Photopheresis (ECP) 

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IND Number 
151546 
NCT Number (CT.gov) 
04446182 
Historical Protocol Version Dates 
Version 1: 31AUG2020 
Version 2: 16JUL2021 
Version 3: 28JAN2022 
 
 
 

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TABLE OF CONTENTS 
Page 
TABLE OF CONTENTS ................................................................................................................ 3 
LIST OF ABBREVIATIONS ......................................................................................................... 7 
PROTOCOL SIGNATURE ....................................................................................................... 10 
STUDY SUMMARY.................................................................................................................... 11 
SCHEMA ...................................................................................................................................... 15 
1 
OBJECTIVES ....................................................................................................................... 16 
1.1 
Primary Objective .......................................................................................................... 16 
1.2 
Secondary Objectives ..................................................................................................... 16 
1.3 
Exploratory Objective(s) ................................................................................................ 17 
2 
BACKGROUND .................................................................................................................. 18 
2.1 
Chronic Graft versus Host Disease ................................................................................ 18 
2.2 
Combination Rationale ................................................................................................... 20 
2.3 
Justification for Dose ..................................................................................................... 20 
2.4 
Dose Rationale for Organ Impairment ........................................................................... 21 
3 
DRUG INFORMATION ...................................................................................................... 22 
3.1 
INCB039110 .................................................................................................................. 22 
4 
STUDY DESIGN.................................................................................................................. 28 
4.1 
Description ..................................................................................................................... 28 
4.2 
Part 1: Dose De-Escalation ............................................................................................ 29 
4.3 
Dose Limiting Toxicity .................................................................................................. 30 
4.4 
Part 2: Dose Expansion .................................................................................................. 31 
4.5 
Number of Patients ......................................................................................................... 32 
4.6 
Number of Study Centers ............................................................................................... 32 
4.7 
Study Duration ............................................................................................................... 32 
5 
ELIGIBILITY CRITERIA.................................................................................................... 33 
5.1 
Inclusion Criteria ............................................................................................................ 33 
5.2 
Exclusion Criteria ........................................................................................................... 35 
5.3 
Recruitment Strategies ................................................................................................... 38 
5.4 
Lifestyle Considerations ................................................................................................. 38 
6 
TREATMENT PLAN ........................................................................................................... 38 

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6.1 
Administration Schedule ................................................................................................ 38 
6.2 
Itacitinib ......................................................................................................................... 40 
6.3 
Extracorporeal Photopheresis ......................................................................................... 41 
6.4 
Concomitant Medications and Therapies ....................................................................... 41 
6.5 
Ancillary Therapy and Supportive Care......................................................................... 41 
6.6 
Prophylaxis for Infectious Diseases ............................................................................... 42 
6.7 
Duration of Therapy ....................................................................................................... 44 
7 
TOXICITIES AND DOSE MODIFICATION ..................................................................... 46 
7.1 
Dose Modifications during the DLT period ................................................................... 46 
7.2 
Dose Interruptions .......................................................................................................... 46 
7.3 
Dose Reductions ............................................................................................................. 46 
7.4 
Guidelines for Management of Adverse Events ............................................................ 47 
7.5 
Supportive Care .............................................................................................................. 49 
8 
SCHEDULE OF EVENTS ................................................................................................... 50 
9 
STUDY PROCEDURES ...................................................................................................... 56 
9.1 
Screening Evaluations .................................................................................................... 56 
9.2 
Treatment Period ............................................................................................................ 56 
9.3 
Disease progression ........................................................................................................ 56 
9.4 
End of Treatment ............................................................................................................ 56 
9.5 
Follow-up Evaluations ................................................................................................... 56 
10 Study Assessments ................................................................................................................ 56 
10.1 
Physical Examinations and Vital Signs ...................................................................... 57 
10.2 
Adverse Events ........................................................................................................... 57 
10.3 
12-Lead Electrocardiograms ....................................................................................... 57 
10.4 
Laboratory Assessments ............................................................................................. 57 
10.5 
HIV and Hepatitis Serologies ..................................................................................... 58 
10.6 
Infection Monitoring................................................................................................... 59 
10.7 
Graft Failure and Chimerism Monitoring ................................................................... 59 
10.8 
Disease Malignancy/Relapse ...................................................................................... 59 
10.9 
Chronic GVHD Assessment ....................................................................................... 60 
10.10 
Pulmonary Function Test............................................................................................ 60 
10.11 
AM-PAC ..................................................................................................................... 60 

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10.12 
2-minute Walk Test .................................................................................................... 60 
11 CRITERIA FOR EVALUATION AND ENDPOINT .......................................................... 60 
11.1 
Safety .......................................................................................................................... 60 
11.2 
Efficacy ....................................................................................................................... 60 
11.3 
Stopping Rules ............................................................................................................ 61 
12 STATISTICAL CONSIDERATIONS.................................................................................. 62 
12.1 
Sample Size Determination ........................................................................................ 62 
12.2 
Population for analyses ............................................................................................... 63 
12.3 
Replacement of Participants ....................................................................................... 63 
12.4 
Statistical Analysis ..................................................................................................... 63 
13 REGISTRATION GUIDELINES ......................................................................................... 67 
14 DATA SUBMISSION SCHEDULE .................................................................................... 67 
15 SPECIAL INSTRUCTIONS ................................................................................................ 67 
15.1 
Correlative Studies ..................................................................................................... 67 
16 ETHICAL AND REGULATORY CONSIDERATIONS .................................................... 68 
16.1 
Human Subject Protections ........................................................................................ 68 
16.2 
Institutional Review .................................................................................................... 68 
16.3 
Data and Safety Monitoring Plan ............................................................................... 68 
16.4 
Adverse Events ........................................................................................................... 69 
16.5 
Serious Adverse Event (SAE) .................................................................................... 70 
16.6 
Deaths ......................................................................................................................... 72 
16.7 
Reporting of Pregnancy .............................................................................................. 72 
16.8 
Protocol Amendments ................................................................................................ 73 
16.9 
Protocol Deviations .................................................................................................... 73 
16.10 
FDA Annual Reporting .............................................................................................. 73 
16.11 
Clinical Trials Data Bank ........................................................................................... 73 
16.12 
Record Keeping .......................................................................................................... 74 
17 BIBLIOGRAPHY ................................................................................................................. 75 
 
List of Figures 
Figure 1: Study Schema ................................................................................................................ 15 
 
List of Tables 

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Table 1: Dose de-escalation Schedule ........................................................................................ 29 
Table 2: 3+3 Dose de-escalation design ..................................................................................... 29 
Table 3: Definition of Dose-Limiting Toxicity.......................................................................... 30 
Table 4: Recommended ECP Schedule ..................................................................................... 39 
Table 5: Itacitinib Dose Levels................................................................................................... 47 
Table 6: Adverse Event Management Guidelines .................................................................... 47 
Table 7: Schedule of Events ....................................................................................................... 51 
Table 8: Laboratory Assessments.............................................................................................. 57 
Table 9: Organ Assessments ...................................................................................................... 61 
Table 10: Post-baseline Response Evaluations ......................................................................... 61 
Table 11: Probability of stopping .............................................................................................. 62 
 
List of Appendices  
Appendix 1: Karnofsky Performance Status ........................................................................... 77 
Appendix 2: NIH Criteria Staging of Chronic GVHD ............................................................ 78 
Appendix 3: Staging of Chronic GVHD ................................................................................... 79 
Appendix 4: NIH Criteria for Response Assessment of Chronic GVHD .............................. 83 
Appendix 5: Clinician Chronic GVHD Activity Assessment .................................................. 84 
Appendix 6: Patient Chronic GVHD Activity Assessment ..................................................... 91 
Appendix 7: AM-PACBasic Mobility Outpatient Routine Short Form ................................ 92 
Appendix 8: Lee Symptom Scale ............................................................................................... 94 
Appendix 9: 36-Item Short Form Survey Instrument (SF-36) ............................................... 96 
Appendix 10: Patient Dosing Diary ......................................................................................... 102 
Appendix 11: AM-PAC Outpatient Conversion Table ......................................................... 104 
 
 

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LIST OF ABBREVIATIONS 
Abbreviation or Term1 
Definition/Explanation 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
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 
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 
eCRF 
Electronic case report form 

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Abbreviation or Term1 
Definition/Explanation 
DLT 
Dose Limiting Toxicity 
ECG 
Electrocardiogram 
Eg 
Exempli Gratia (for example) 
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-glutamyltransferase 
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 
The lower limit of quantitation 
MedDRA 
Medical Dictionary for Drug Regulatory Activities 
MRI 
Magnetic resonance imaging 
MRSD 
The maximum recommended starting dose 
MTD 
Maximum tolerated dose  

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Abbreviation or Term1 
Definition/Explanation 
NOAEL 
No-observed-adverse-effect level 
NOEL 
No-observed-effect-level 
PD 
Pharmacodynamic(s) 
PFS 
Progression-Free Survival 
PFT 
Pulmonary Function Test 
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 Fridericia equation 
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 
The upper limit of normal 
ULQ 
The 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 the protocol.  
 

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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 multi-site 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 
 
 

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STUDY SUMMARY 
Title 
A Phase 2 Study of Itacitinib (INCB039110) and Extracorporeal 
Photopheresis (ECP) for First-line Treatment in Chronic Graft-
versus-Host Disease 
Short Title 
FLIGHT 
Protocol Identifiers  
(IRB – internal) 
HCI IRB #130090 
IND number 
IND # 151546 
Phase 
Phase 2 
Design 
This is a multisite, single-arm, open-label Phase II study of oral 
itacitinib in combination with extracorporeal photopheresis in 
subjects with moderate to severe chronic GVHD. Part 1 will 
utilize a standard 3+3 design to evaluate the safety of daily oral 
itacitinib in combination with ECP.  Part 2 is an expansion phase 
and patients will be treated with itacitinib in combination with 
ECP to determine its clinical efficacy in the treatment of 
moderate-severe chronic GVHD. 
Study Duration 
 
Part 1: 6-18 months  
 
Part 2: 2-3 years 
Study Center(s) 
This study will be conducted at the Huntsman Cancer Institute and 
up to 3 additional cancer centers 
Objectives 
Primary Objective: 
 
Part 1: To assess an appropriate dose of itacitinib in 
combination with Extracorporeal Photopheresis (ECP) in 
patients with moderate or severe chronic GVHD. 
 
Part 2: To assess the clinical efficacy of itacitinib in 
combination with ECP in subjects with moderate or severe 
chronic GVHD treated at the Recommended Phase 2 Dose 
(RP2D). 
Secondary Objectives: 
 
To assess the safety of itacitinib in combination with ECP. 
 
To assess long term response and efficacy. 
Number of Subjects 
6 to 18 patients being evaluated in Part 1. 
40 subjects enrolled in Part 2. 
Diagnosis and Main 
Eligibility Criteria 
Key Inclusion Criteria: 
 
Active, clinically diagnosed, moderate or severe chronic 
GVHD as defined by the NIH Consensus Development 
Project Criteria.  

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 
History of an allogeneic hematopoietic cell transplant for any 
hematologic disorder with any conditioning regimen, donor, 
or graft source. 
 
Need for systemic treatment for chronic GVHD. 
 
No previous systemic treatment for chronic GVHD. 
 
Prior ECP for the treatment of acute GVHD is allowed, 
however, ECP must have occurred > 4 weeks prior to Cycle 1 
Day 1. 
Key Exclusion Criteria: 
 
Subjects with score 3 lung GVHD or biopsy-proven 
bronchiolitis obliterans.  
 
Uncontrolled manifestations of acute GVHD. 
 
Received prior JAK inhibitor therapy for any indication ≤ 4 
weeks prior to Cycle 1 Day 1. 
 
Received any previous systemic treatment for chronic GVHD. 
 
Relapsed or progressive malignant disease or any post-
transplant lymphoproliferative disease 
 
Treatment with any other investigational agent, device, or 
procedure, within 30 days of enrollment 
 
Inability swallow food or any condition of the upper 
gastrointestinal tract that precludes administration of oral 
medications 
 
Uncontrolled infections 
Study Product, Dose, 
Route, Regimen 
Treatment will initiate at 200 mg daily of itacitinib (Cohort 1). If 
unacceptably high DLTs are observed, the itacitinib dose can be 
sequentially reduced to 100 mg oral daily (Cohort -1) and then 100 
mg oral every other day (Cohort -2). Patients in Part 1 who do not 
experience a DLT are permitted to continue treatment at their 
initial dose.  
 
ECP will be given at a frequency of twice weekly for 8 weeks 
followed by a standard taper schedule as per study protocol if 
there is a response.  
Duration of 
administration 
Treatment with itacitinib will be administered continuously until 
the end of week 24 or until treatment discontinuation criteria is 
met. Patients with PR or better may continue itacitinib for up to 1 
year. 

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Reference therapy 
Reference therapy is systemic steroids. We are comparing 
historical response rates to high dose steroids. 
Statistical Methodology 
Simon’s optimal two-stage design will be used in Part 2. The 
primary outcome is the overall response rate (CR + PR) at 24 
weeks. Withdrawal or progression prior to 24 weeks or missing 
24-week assessment will be considered non-response. After the 
first 16 patients treated at the RP2D complete 24 weeks of therapy 
or meet treatment discontinuation criteria, enrollment will be put 
on hold and an interim analysis will be conducted. This study 
treatment will be considered promising if the overall response rate 
at 24 weeks is ≥ 60% and unacceptable if the overall response rate 
at 24 weeks is ≤40%. 50% is the reported best overall response 
rate of current first-line therapy with high-dose steroids. The null 
hypothesis that the true response rate is ≤ 40% will be tested 
against a one-sided alternative.  
In the first stage of the dose-expansion study, 16 patients will be 
accrued and followed through the first 24 weeks of treatment. Of 
those 16 patients, 6 patients will be carried over from Part 1 at the 
RP2D. In recognition of a potential accrual pause of at least 24 
weeks, if all 16 patients are required to complete six months of 
combination therapy, we will permit enrollment of an additional 3 
patients (20%) after the first 10 eligible patients in the first stage 
of the dose-expansion study are enrolled if no more than 5 of 16 
patients have experienced treatment failure (i.e. addition of 
secondary systemic therapy or disease relapse or death) by the end 
of week 12 of treatment. If there are 7 or fewer responses in the 
first 16 patients enrolled, the study will be stopped. Otherwise, 30 
additional patients will be accrued for a total of 46. The null 
hypothesis will be rejected if 24 or more responses are observed in 
46 patients. This design yields a type I error rate of 0.0486 and a 
power of 80% when the true response rate is ≥ 60%.  
To protect patient safety, an early stopping rule for toxicity will be 
implemented in Part 2. A 20% rate of DLT will be considered 
acceptable and a 30% rate of DLT would be unacceptable. The 
trial will be stopped if more than 3/9, 4/13, 5/17, 6/21, 7/26, 8/31, 
9/36, 10/40, or 11/45 patients experience grade 3 or higher non-
hematologic adverse events attributed to study therapy.  Response 
assessments will occur every month for the first 24 weeks. The 
primary efficacy endpoint will be evaluated at 24 weeks. Patients 
with responding disease may continue therapy for another 24 
weeks.  
Toxicity in this trial will be defined as DLTs as described in 
Section 4.3, attributed to the study therapy. A safety analysis will 
be conducted on the safety population, which includes enrolled 

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subjects who receive at least 1 dose of itacitinib and one ECP 
treatment.  

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SCHEMA 
 
 
 
 
Figure 1: Study Schema 
 
 

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1 
OBJECTIVES 
1.1 
Primary Objective 
1.1.1 Part 1: To assess an appropriate dose of itacitinib in combination with 
Extracorporeal Photopheresis (ECP) in patients with moderate or severe chronic 
GVHD. 
Primary Endpoint: The rate of dose-limiting toxicities during the defined DLT 
evaluation period. 
1.1.2 Part 2: To assess the clinical efficacy of itacitinib in combination with ECP in 
subjects with moderate or severe chronic GVHD treated at the Recommended 
Phase 2 Dose (RP2D). 
Primary Endpoint: Overall response rate (ORR) at 24 weeks (at Cycle 7 Day 1 
visit) as determined by the NIH Consensus Development Project Criteria (ORR 
is defined as CR + PR) without secondary systemic immunosuppressive therapy 
and no recurrent malignancy or death. 
1.2 
Secondary Objectives 
1.2.1 To assess the safety of itacitinib in combination with ECP. 
Secondary Endpoint: Frequency of adverse events (AEs) and serious adverse 
events (SAEs) will be collected assessed by CTCAE, version 5.0 for the 
duration of treatment. 
1.2.2 To assess long term response and efficacy. 
Secondary Endpoints: 
 Overall response rate at 1-year as determined by the NIH Consensus 
Development Project Criteria, without secondary systemic 
immunosuppression and no recurrent malignancy or death 
 Failure Free Survival (FFS) at 24 weeks and 1-year as defined as the 
time from the initiation of study therapy until treatment failure defined as 
the initiation of secondary therapy for chronic GVHD, malignancy 
relapse, or death from any cause.  
 The proportion of patients who have withdrawn all immunosuppressants 
at 1-year. 
 Overall response rate at 24 weeks, as determined by the NIH Consensus 
Development Project Criteria, stratified by concurrent prednisone (or 
equivalence) use: 0 mg/kg/d, ≤ 0.25mg/kg/d, and > 0.25mg/kg/d. 
 The mean cumulative prednisone dose used up to 24 weeks. 

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 Organ-specific response rates at 24 weeks and 1-year as determined by 
the NIH Consensus Development Project Criteria. 
 Change in NIH global score of chronic GVHD from baseline to 24 
weeks and 1-year after the initiation of the protocol therapy. The NIH 
global score will be defined by using the NIH consensus criteria for the 
assessment of chronic GVHD severity. 
 Duration of response (DOR), defined as the interval between the date of 
initial documentation of a response (PR or better), and the time of 
progression from the best response, the start of a new therapy for 
cGVHD (including corticosteroids), or death from any cause. 
 Clinician-reported chronic GVHD activity assessment at baseline, 24 
weeks, and 1-year.  
 Patient-reported chronic GVHD severity assessment at baseline, 24 
weeks, and 1-year. 
 24 week and 1-year non-relapse mortality (NRM) defined as the 
proportion of participants who died due to causes other than a relapse of 
their primary hematologic disease. 
 Relapse rate (RR) of malignant and non-malignant hematologic diseases, 
defined as the proportion of participants whose underlying disease 
relapses at 24 weeks and 1-year.  
 Overall survival (OS) as defined as the time from the initiation of study 
therapy until death from any cause at 24 weeks and 1-year.  
1.3 
Exploratory Objective(s) 
1.3.1 To assess patient-reported outcomes. 
Exploratory Endpoint: The change in symptom scores using the QOL-SF-36-v2 
questionnaire, Lee Chronic GVHD Symptom Scale, and the Activity Measure 
for Post Acute Care (AM-PAC) Basic Mobility Outpatient Routine Short Form 
at 24 weeks and 1-year. 
1.3.2 To explore pharmacodynamic characteristics of itacitinib. 
Exploratory Endpoint: inhibition of JAK1 and STAT phosphorylation in 
response to relevant cytokines, when administered in combination with ECP in 
subjects with chronic GVHD. 
1.3.3 To describe possible biomarkers pre- and post-treatment.  
Exploratory Endpoint: changes in T-cell subsets, B-cell population, cytokine 
expression, and other biomarkers of chronic GVHD. 

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1.3.4 To explore associations between socioeconomic factors and outcomes 
Exploratory Endpoint: change in residence, annual income, insurance type, 
employment status from pre- and post- treatment. 
2 
BACKGROUND 
2.1 
Chronic Graft versus Host Disease 
Allogeneic Hematopoietic Cell Transplantation (AlloHCT) is a potentially curative treatment 
modality for patients with hematologic disorders who would otherwise have a poor outcome 
with other conventional treatment approaches alone. AlloHCT causes donor-derived immune 
responses that can result in the desired graft-versus-tumor effect as well as the undesired 
complication, Graft versus Host Disease (GVHD). In the United States, approximately 8,000 
alloHCTs are now performed each year1. Chronic GVHD is the main complication for long-
term survivors of a successful alloHCT and it occurs in 30% to 70% of all patients who 
undergo an alloHCT and in the majority of patients who develop acute GVHD as a 
complication of their alloHCT2. Roughly 35% of patients who have undergone alloHCT 
develop chronic GVHD that requires systemic treatment3. Chronic GVHD is a serious and 
life-threatening condition to the otherwise curative potential of HCT and it is the leading 
cause of non-relapse mortality (NRM)2, 4. The prevalence of chronic GVHD is increasing due 
to both the increased use of alloHCT in older adults and the use of peripheral blood stem 
cells as a graft source. Other risk factors for developing chronic GVHD include prior acute 
GVHD, use of unrelated and mismatched donors, and lack of T-cell depletion4.  
In the past, GVHD was classified into two subsets depending on the timing of manifestations 
of GVHD. Acute GVHD was classified as occurring within 100 days of HCT and chronic 
GVHD classified as manifestations beyond 100 days after HCT5. In 2005, the National 
Institute of Health (NIH) developed Chronic GVHD Consensus Criteria to propose new 
criteria for the diagnosis and classification of chronic GVHD for clinical trials5. Minor 
revisions to the diagnostic criteria of acute and chronic GVHD were proposed in a follow-up 
consensus conference in 20146. The diagnosis of chronic GVHD requires at least one 
diagnostic sign in a target organ per NIH criteria (i.e., a sign found only in chronic GVHD) 
or at least one distinctive sign (i.e., a sign highly suggestive of chronic GVHD) in 
combination with some other laboratory, biopsy, or other test confirmation in the same or 
another organ. The diagnostic chronic GVHD findings include collagen-vascular changes 
involving the skin, mouth, genitalia, gastrointestinal tract, lung, muscle fascia, and joints. 
Pathologically, chronic GVHD is characterized by fibrosis and inflammation of affected 
organs7. 
2.1.1 Current Treatment Options 
The mainstay of first-line immunosuppressive therapy in patients with chronic GVHD 
is systemic glucocorticoids. Systemic glucocorticoids have limited efficacy and 
significant long-term complications, including frequent infections, hypertension, 
hyperglycemia, a decrease in bone density, avascular necrosis, adrenal insufficiency, 
cataracts, and disturbed sleep patterns. More than 50% of patients treated with 
corticosteroids eventually relapse or become refractory, requiring second-line treatment. 

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Despite the many alternative immunosuppressive agents to systemic glucocorticoids, no 
single class of immunosuppressive agents has persistently produced a steroid-sparing 
effect in patients with chronic GVHD2. In conclusion, chronic GVHD and its current 
standard therapy have a major negative impact on the quality of life (QoL) and survival 
in patients in whom allogeneic HCT was able to achieve a cure from their original 
hematologic malignancy. Therefore, there is a desperate need for more effective agents 
in treating chronic GVHD. 
2.1.2 Role of JAK Pathway in Chronic GVHD 
The Janus kinase (JAK) 1 and 2 pathway has been implicated in the pathway of both 
acute and chronic GVHD. Choi et al.8 showed a role for both JAK1 and JAK2 as 
mediators of interferon-gamma receptor signaling which regulates alloreactive T cell 
trafficking to GVHD target organs through CXCR3 expression in alloreactive T cells 
after allogeneic HCT. In the chronic GVHD setting, inhibition of JAK has multimodal 
effects and includes reduced proliferation of effector T cells and suppression of pro-
inflammatory cytokines that are associated with inflammation, tissue damage, and 
fibrosis; promotion of tolerogenic T cells; and impaired function of dendritic cells 
resulting in decreased alloreactive T cell activation9, 10. Ruxolitinib, a selective JAK1/2 
inhibitor, has shown efficacy in the treatment of GVHD in several preclinical murine 
studies8, 9, 11 without interfering with the beneficial graft-versus-leukemia (GVL) effect8, 
12. Retrospective studies in human subjects have suggested that JAK 1/2 inhibition with 
ruxolitinib treatment provides clinical benefit with favorable safety and preservation of 
the GVL effect in heavily pre-treated patients with steroid-refractory acute and chronic 
GVHD13, 14. Based on these observations, phase 2 and 3 clinical trials evaluating 
ruxolitinib for the treatment of steroid-refractory acute and chronic GVHD following 
allogeneic HCT were conducted. Ruxolitinib therapy was found to improve efficacy 
outcomes in both steroid-refractory acute15 and chronic16 GVHD and was thereafter 
FDA-approved for both indications.  
Itacitinib, INCB039110, is a selective and potent JAK1 inhibitor. It has shown similar 
pharmacologic inhibition of interferon signaling, resulting in the decreased expression 
of CXCR3 and reduced GHVD. It has been studied in combination with corticosteroids 
in grades IIB-IVD treatment-naïve acute GVHD in a randomized phase 3 study. While 
the study showed no statistical difference in response rates between the itacitinib and 
corticosteroid treatment arm versus control group, the safety profile was acceptable. 
2.1.3 Role of Extracorporeal Photopheresis (ECP) in Chronic GVHD 
Extracorporeal Photopheresis (ECP) is an immunomodulatory treatment that involves 
ex vivo collection of mononuclear cells from peripheral blood, exposure to the 
photoactive agent 8-methoxy psoralen, ultraviolet radiation and re-infusion of the 
processed cell product into the patient17. Although not FDA-approved for the treatment 
of GVHD, its clinical benefits in steroid-refractory chronic GVHD (SR-cGHVD) have 
been well documented18. In addition, two systematic reviews of studies evaluating ECP 
for SR-chronic GVHD revealed pooled overall response rates (ORR) of 64% (95% CIs, 
47%-79%19 to 65%-82%20). Its mechanisms of action in SR-cGVHD remains unclear 
but a number of immunomodulatory properties have been proposed, including direct 

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damage to pathogenic immune cells via apoptosis induction, impaired antigen 
presentation and antigen-presenting cell activation, increased prevalence of natural 
killer cells, differentiation to and modulation of circulating dendritic cells, and skewing 
of Th1 toward Th2 responses. Lastly, ECP is a well-tolerated procedure with rare side 
effects, allowing avoidance of necessary treatment modifications or discontinuation18. 
While ECP has been examined as second-line treatment for SR-chronic GVHD, it has 
yet to be evaluated as first-line therapy for patients with newly diagnosed chronic 
GVHD. 
2.2 
Combination Rationale 
While corticosteroids are effective in some patients, there are no approved therapies for first-
line treatment of chronic GVHD as no other immunosuppressant therapy has proven to be 
effective. Furthermore, systemic glucocorticoids are wrought with long term-complications, 
thereby increasing morbidity and mortality in this patient population who are otherwise cured 
of their original malignancy. Therefore, there is increased interest to identify treatments that 
provide long-term control of chronic GVHD while sparing the need for systemic steroids.  
Both itacitinib and ECP have shown anti-inflammatory and immunomodulatory effects in 
GVHD. It has not yet been determined if the mechanism of action of each therapy is similar.  
However, it is possible that their effects may complement each other and enhance the 
dampening of the pro-inflammatory environment present in chronic GVHD.  
Both itacitinib and ECP have not been independently studied for front-line treatment of 
chronic GVHD. Jak 1/2 inhibition has a very high response rate and steroid-sparing capacity 
in acute GVHD. It is currently under study in clinical trials as treatment for steroid-refractory 
chronic GVHD. Itacitinib is also currently being evaluated in clinical trials for first-line 
treatment of newly diagnosed moderate to severe chronic GVHD. The overall safety profile 
of itacitinib has been shown to be favorable as demonstrated in a phase 3 randomized clinical 
trial of itacitinib for treatment-naïve acute GVHD. ECP, on the other hand, is one of the most 
effective second-line therapies for chronic GVHD and also has steroid-sparing properties. 
These findings support the clinical evaluation of combination therapy with itacitinib and ECP 
as a first-line treatment option for patients with chronic GVHD.   
2.3 
Justification for Dose 
In a Phase 1 study (INCB 39110-108) that assessed the safety and tolerability of itacitinib in 
combination with corticosteroids, 30 acute GVHD participants were randomized to 1 of 2 
treatment cohorts (200 mg cohort, n = 14; 300 mg cohort, n = 16).  The Day 28 ORR in first-
line acute GVHD participants in both treatment cohorts was 83.3%; for participants with 
steroid-refractory acute GVHD, the ORR at Day 28 was 64.7% (200 mg cohort, 62.5%; 300 
mg cohort, 66.7%).  One DLT of Grade 3 thrombocytopenia was reported in 1 participant 
with pre-existing thrombocytopenia who was randomized to the 300 mg cohort.  Adverse 
events reported in greater than 20% of all participants include diarrhea, hypokalemia, 
peripheral edema, hyperglycemia, abdominal pain, hypophosphatemia, fatigue, headache, 
hypomagnesemia, and sepsis.  Thrombocytopenia and platelet count decreased were 
observed in 24.2% and 20.7% of participants, respectively, with a higher proportion of these 
events occurring in the 300 mg cohort, although a higher incidence of pre-existing 

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thrombocytopenia was also observed in this group.  Among both dose groups (200 mg and 
300mg daily), itacitinib was generally well-tolerated with an AE profile as expected. 
Mild decreases in platelet count of 5000-10,000/mcl is expected to occur following a 
scheduled ECP session. As itacitinib 300 mg daily has been reported to have a higher 
incidence of thrombocytopenia/platelet decrease as compared to itacitinib 200 mg daily, we 
will test the combination of ECP with itacitinib 200 mg daily. 
Dose Modifications for Concomitant Medications 
Observed data from Study INCB 39110-108 suggest that there is an approximately 2-fold 
increase in exposure when itacitinib is co-administered with a potent CYP3A4 inhibitor.  In a 
healthy volunteer study, co-administration of itacitinib 200 mg with itraconazole 200 mg QD 
resulted in a nearly 5-fold increase in exposure.  This discrepancy may be due to the fact that 
at the time of steady-state PK determination, all of the participants in INCB 39110-108 
except 1 were on posaconazole, a less potent inhibitor than itraconazole based on midazolam 
fold change.  A PBPK model was used to simulate an itacitinib 100 mg QD dose when co-
administered with itraconazole.  The resulting exposure (2306 nM∙h) approximates that 
observed in GVHD patients taking 300 mg QD alone (2855 nM∙h).  Therefore, it is 
recommended that participants do not take the following potent CYP3A4 inhibitors while on 
itacitinib:  itraconazole, voriconazole, mibefradil, and clarithromycin.  No dose modification 
is recommended for concomitant administration of CYP3A4 inhibitors less potent than 
itraconazole, for example, posaconazole. The solubility of itacitinib is > 1.10 mg/mL (and 
therefore > 200 mg/250 mL or 300 mg/250 mL) at pH values up to 4.3.  In most cases of 
treatment with gastric acid-reducing agents, the target pH is approximately 4, and in those 
situations, there should not be any significant impact on the absorption of itacitinib.  The lack 
of impact of gastric pH–modifying agents was supported through graphical analysis and 
modeling of observed data along with PBPK model.  No dose modification of itacitinib is 
recommended in participants concomitantly taking gastric pH modifying agents.  
2.4 
Dose Rationale for Organ Impairment 
A preliminary population PK model indicates that mild hepatic impairment has no impact on 
the PK of itacitinib.  Therefore, no dose modification is recommended in patients with mild 
hepatic impairment.  Data are insufficient to evaluate the impact of moderate or severe 
hepatic impairment using a modeling approach.  Given the limited data in patients with 
moderate to severe hepatic impairment, while acknowledging several participants from Study 
INCB 39110-108 did have severe hepatic impairment with no significant impact on itacitinib 
PK, no dose modification is recommended in patients with moderate hepatic impairment.  
Patients with hepatic impairment not due to chronic GVHD (i.e., those with persistent total 
bilirubin > 2 mg/dL) are excluded.  Patients with hepatic impairment due to chronic GVHD 
may potentially benefit from study treatment, with an improvement of their liver function.  
The benefit from treatment could outweigh the risk in these patients; therefore, patients with 
hepatic impairment due to chronic GVHD may be enrolled in the study under close 
monitoring for response to treatment and liver function improvement. The population PK 
model indicates that there is also no impact of mild or moderate renal impairment on the PK 
of itacitinib.  Therefore, no dose adjustment is recommended in patients with mild or 

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moderate renal impairment.  Patients with severe renal impairment, that is, creatinine 
clearance ≤ 30 mL/min, are excluded from the study. 
3 
DRUG INFORMATION 
3.1 
INCB039110 
Itacitinib adipate (INCB039110 adipate), referred to herein as itacitinib, is a novel, potent, 
and selective inhibitor of the Janus kinase (JAK) family of protein tyrosine kinases (TYKs) 
with selectivity for JAK1 and with low in vitro affinity for JAK2. Itacitinib is an 
investigational product that is proposed for development for the treatment of 
myeloproliferative neoplasms (MPNs), including myelofibrosis (MF); inflammatory disease, 
including rheumatoid arthritis (RA) and psoriasis; graft-versus-host disease (GVHD); solid 
tumors; and B-cell malignancies. Janus kinases play an important role in signal transduction 
following cytokine and growth factor binding to their receptors. Aberrant production of 
cytokines and growth factors has been associated with MPNs and a number of chronic 
inflammatory conditions, and JAK1 has been shown to cooperate with other JAKs to mediate 
the signaling of a number of inflammatory cytokines. Therefore, JAK inhibitors represent 
potential therapeutic agents for these disease states. Itacitinib is proposed for investigation 
and development for the treatment of chronic GVHD. 
3.1.1 Pharmacology Summary 
Itacitinib represents a novel, potent, and selective inhibitor of the JAKs with selectivity 
for JAK1. There are 4 known JAK family members, JAK1, JAK2, JAK3, and TYK2. 
Additional details on the pharmacology and toxicology of itacitinib are described in the 
IB. In brief, itacitinib potently inhibitors JAK1 (IC50 = 3.6 nM) with 22- to > 500-fold 
selectivity compared with JAK2, JAK3, and TYK2, and it does not significantly inhibit 
a broad panel of approximately 60 other kinases. Itacitinib is potent (IC50 values 10 nM 
to 100 nM) in cytokine-driven cell-based assays, such as IL-2-stimulated 
phosphorylation of JAKs and STATs and IL-2-induced proliferation of primary human 
T cells. Itacitinib inhibits the growth of the cytokine-dependent cell line INA-6 and this 
effect is not due to general cytotoxicity. Itacitinib potently inhibits the phosphorylation 
of STAT proteins and the production of proinflammatory factors (e.g., IL-17, MCP-1) 
induced by cytokines such as IL-23 and IL-6 (IC50~30-100 nM).  In contrast, itacitinib 
shows less inhibition in cell-based assays dependent on JAK2 (e.g., TPO or prolactin-
stimulated STAT phosphorylation) with IC50 approximately 1uM or greater, suggesting 
that itacitinib is JAK2-sparing in cells. In in vivo models of JAK-dependent malignancy, 
itacitinib impedes subcutaneous tumor growth of INA-6 cells expressing wild-type 
JAKs plasma concentrations well below those necessary to inhibit JAK2 V617F-driven 
neoplasia model of MF.  
Itacitinib administration is highly effective in both prophylactic (Day -3) and 
therapeutic (Day 14) regimens in ameliorating body weight loss and improving GVHD 
scores and has no detrimental effects on engraftment in an MHC-mismatched mouse 
model of acute GVHD (acute GVHD). Maximal upregulation of TH1 relevant cytokines 
in this model is observed in the colon on Day 28, and significant reduction in cytokine 

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profiles (IFNγ, TNFα, and IL1β) in the diseased colon tissue os observed with itacitinib 
120 mg/kg treatment. Itacitinib effectively reduces the CD4+ and CD8+ T cells in the 
colon on Day 28 and downregulate CD3+/pSTAT3+ and total pSTAT3+ expression.  
Itacitinib did not demonstrate off-target activity or any activity in a number of non-JAK 
family kinases. Administration of itacitinib did not result in QT prolongation or 
cardiovascular effects. Adverse findings were noted only at high dose (1000 mg/kg) 
suggesting the primary toxicities are expected to be on-target and these observations are 
considered to be well beyond the needed safety margin compared to the therapeutic 
dose. 
In summary, pharmacological data obtained in both in vitro and in vivo model systems 
support the potential utility of orally administered itacitinib in the treatment of chronic 
GVHD. 
3.1.2 Nonclinical Drug Metabolism and Pharmacokinetics 
In single-dose PK studies in rats, dogs, and monkeys, orally administered itacitinib was 
rapidly absorbed (tmax ≤ 2.0 hours). The protein binding of itacitinib in plasma and 
serum from rats, dogs, and humans was moderate (unbound fraction of 29%-43%) and 
not dependent on itacitinib concentration.  
Itacitinib has minimal penetration across the blood-brain barrier in rats. Protein binding 
in plasma and serum from rats, dogs, and humans was moderate, and the fraction 
unbound was independent of itacitinib concentration. In rats and dogs, excretion was 
rapid and complete after a single oral dose of 14C-INCB039110. 
The major analyte present in plasma and urine from all species studies was parent 
compound. CYP3A4 is the major isozyme responsible for the metabolisms of itacitinib. 
Itacitinib did not inhibit or induce CYP activity, suggesting a low potential for drug-
drug interactions. 
Preliminary PK analysis showed that following multiple-dose administration of 
itacitinib SR formulation, itacitinib attained peak plasma concentrations with a median 
tmax of 1.89 hours to 3.78 hours. For increasing dose regimens between 100 mg BID 
and 200 mg BID, itacitinib plasma exposures (Cmax and AUC) appeared to be dose-
proportional. The itacitinib AUC for 600 mg QD in subjects with PMF, PPV-MF, and 
PET-MF was comparable to that of 600 mg QD in subjects with stable, chronic plaque 
psoriasis. 
Additional information on pharmacology, drug disposition, and nonclinical toxicology 
is available in the itacitinib IBv10.  
3.1.3 Preclinical Summary of INCB039110 
The preclinical pharmacokinetics (PK) of INCB039110 was evaluated in rats, dogs, and 
monkeys. INCB039110 exhibits low-to-moderate systemic clearance, a low volume of 
distribution, and a short terminal elimination half-life. The oral bioavailability was low 
in monkeys (<20%), moderate in dogs (43%), and high in rats (82%). The in vitro 
permeability of INCB039110 across Caco-2 monolayers was low to moderate. 
INCB039110 is mainly cleared by metabolism and is a substrate of cytochrome P450 

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(CYP) 3A4 but does not significantly inhibit the activity of the major CYP enzymes, 
suggesting that the potential for INCB039110 to cause clinical drug-drug interactions 
through CYP inhibition is low. 
The toxicology profile of INCB039110 was characterized in single- and multiple-dose 
oral studies of up to 6 months in duration in rats and 9 months in dogs. 
Single oral doses of INCB039110 up to 2000 mg/kg in rats and 1000 mg/kg in dogs 
produced no adverse effects. 
Pharmacology-related clinical pathology and anatomical alterations in repeat-dose rat 
studies included a reversible lowering of white blood cell (WBC) count, primarily 
because of a lower circulating lymphocyte count, and reversible lymphoid depletion in 
lymphoid tissues and reduction in bone marrow cellularity. The NOAEL in the 1-, 3-, 
and 6-month rat studies were determined to be 225 mg/kg per day, 300 mg/kg per day, 
and 300 mg/kg per day, respectively.  
In repeat-dose studies in dogs, gastrointestinal inflammation and/or demodicosis were 
dose-limiting. In the 3-month study, gastrointestinal inflammation was the main dose-
limiting toxicity (DLT) leading to early termination (50 mg/kg per day); in the 6-month 
study, gastrointestinal inflammation and demodicosis contributed to early termination 
(50 mg/kg per day); and in the 9-month study, early termination (30 and 40 mg/kg per 
day) was due to demodicosis (gastrointestinal inflammation was not observed). The 
NOAELs determined for the 1-, 3-, 6-, and 9-month studies were, 60 mg/kg per day, 30 
mg/kg per day, 30 mg/kg per day, and 10 mg/kg per day, respectively. 
Like the rat, many of the toxicities observed in repeat-dose dog studies were attributed 
to pharmacology (inhibition of JAK), including the following: decrease in red cell mass 
and/or lymphocytes; increases in WBCs, neutrophils and/or monocytes; decreases in 
cytotoxic T cells; lymphoid depletion in lymphoid tissues; extramedullary 
hematopoiesis in spleen; bone marrow hypocellularity; inflammation/infiltrates in 
various tissues/organs; and demodicosis. 
INCB039110 was not genotoxic in the bacterial mutagenicity assay, the in vitro 
chromosome aberration assay in human lymphocytes, or the in vivo micronucleus assay 
in rats. 
INCB039110 also did not demonstrate off-target activity nor was it active in a panel of 
approximately 60 non-JAK family kinases. Additional information on pharmacology, 
drug disposition, and nonclinical toxicology is available in the itacitinib IBv10. 
3.1.4 Clinical Studies in Patients 
As of the data cutoff date (30 APR 2021), 34 clinical studies with itacitinib (18 Phase 1, 
7 Phase 1/2, 7 Phase 2, and 2 Phase 3), including studies of itacitinib as monotherapy 
and in combination with chemotherapeutic agents, corticosteroids, CNI-based 
interventions, pembrolizumab (anti–PD-1 monoclonal antibody), tyrosine kinase 
inhibitors (ibrutinib and osimertinib), investigational PI3Kδ (INCB040093 and 
parsaclisib), a JAK inhibitor (ruxolitinib), and an IDO1 (epacadostat) inhibitor, have 
either been completed or are ongoing. Table 7 presents all completed and ongoing 
studies with itacitinib and includes studies in MF, GVHD, hematologic malignancies, 

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inflammation, and solid tumors. In addition, a rollover study has been initiated for 
participants who were continuing to receive benefit from treatment with itacitinib at the 
time of their study's closure. As of the cutoff date, approximately 1699 unique 
participants, which includes 543 healthy adult participants, have been exposed to 
itacitinib.  
Additional details regarding the study designs and primary endpoints of these studies 
are summarized in the itacitinib IBv14.  
3.1.5 Itacitinib in Subjects with Acute Graft-Versus-Host Disease 
In the study INCB 39110-108, 29 subjects with acute GVHD received itacitinib in 
combination with corticosteroids (prednisone or methylprednisolone). A summary of 
TEAEs reported in at least 20% of participants is presented in Table 20 of the itacitinib 
IBv14. All participants had at least 1 TEAE. The most frequently reported TEAEs (≥ 
30% of participants) were consistent with expectations for participants with aGVHD and 
included thrombocytopenia/platelet count decreased, diarrhea, edema peripheral, 
abdominal pain, anemia, hypokalemia, hyperglycemia, and fatigue. Nine participants 
(31.0%) had fatal TEAEs; fatal TEAEs reported for more than 1 participant included 
multiorgan failure (3 participants, 10.3%) and respiratory failure and sepsis (2 
participants each, 6.9%). Serious TEAEs were reported in 22 participants (75.9%). The 
most frequently reported serious TEAE was sepsis (5 participants, 17.2%). Other serious 
TEAEs reported in more than 1 participant included acute kidney injury, diarrhea, GI 
hemorrhage, and multiple organ dysfunction syndrome, (3 participants each, 10.3%), and 
respiratory failure, abdominal pain, staphylococcal infection, acute respiratory distress 
syndrome, and thrombocytopenia (2 participants each, 6.9%). Sixteen of the 29 
participants (55.2%) discontinued because of a TEAE. The most frequently reported 
TEAE leading to permanent discontinuation of itacitinib was thrombocytopenia (4 
participants, 13.8%). The only other TEAEs leading to permanent discontinuation of 
itacitinib in more than 1 participant were neutrophil count decreased and sepsis (3 
participants each, 10.3%). 
3.1.6 Itacitinib in Subjects with Chronic Graft-Versus-Host Disease 
As of the data cutoff date, 79 participants who received an allogeneic HSCT and 
developed cGVHD in Study INCB 39110-309 had received at least 1 dose of itacitinib 
in combination with corticosteroids and 16 participants received treatment with 
corticosteroid monotherapy. Seven participants (7.4%) completed study treatment, 29 
participants (30.5%) discontinued study treatment, and 59 participants (62.1%) were 
still receiving study treatment. A summary of TEAEs reported in at least 10% of 
participants is presented in Table 24 of the itacitinib IBv14. Seventy-five participants 
(78.9%) reported at least 1 TEAE. According to preliminary data, TEAEs reported for 
more than 15% of participants in this study were anemia (22 participants, 23.2%); 
diarrhea, hypertension, and platelet count decreased (16 participants each, 16.8%); and 
pyrexia (15 participants, 15.8%). Thirty-four participants (35.8%) experienced serious 
TEAEs. Serious TEAEs reported in more than 2 participants were pyrexia (7 
participants, 7.4%) and chills, diarrhea, pneumonia, and sepsis (3 participants each, 
3.2%). Five participants (5.3%) had fatal TEAEs (myocardial infarction and aspiration 

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[1 participant], febrile neutropenia and pneumonia fungal [1 participant], and veno-
occlusive disease, sudden death, and sepsis [1 participant each]). Thirteen participants 
(13.7%) experienced TEAEs that led to discontinuation of itacitinib treatment; the only 
TEAEs leading to discontinuation reported in more than 1 participant were platelet 
count decreased and pneumonia fungal (2 participants each). 
3.1.7 Extracorporeal Photopheresis (ECP) 
Extracorporeal photopheresis (ECP) is a procedure that involves collecting blood 
outside the patient’s body and exposing extracorporeally circulating leukocyte-enriched 
blood to UVA energy in the presence of the photoactive drug methoxsalen. In the 
photopheresis process, the patient is connected to a photopheresis system via a venous 
catheter interface. Red blood cells are separated from the white blood cells and plasma 
by centrifugation. Red blood cells and excess plasma are returned to the patient while 
the leukocyte-enriched blood (buffy coat) and some plasma are collected in the 
photoactivation bag. UVADEX™ (methoxsalen) Sterile Solution is added to the buffy 
coat in the photoactivation bag, and the UVADEX™ treated buffy coat is then exposed to 
UVA radiation and reinfused into the patient. UVAR ®, UVAR XTS ®, and 
THERAKOS® CELLEX® are the first-, second- and third-generation photopheresis 
systems. 
3.1.8 Oral Methoxsalen and UVADEXTM (methoxsalen) Sterile Solution 
Methoxsalen was first developed as an oral formulation and approved for the palliative 
treatment of cutaneous T-cell lymphoma (CTCL).  A more recent formulation, 
UVADEX™ (methoxsalen) Sterile Solution, is a liquid methoxsalen for ex vivo use in 
ECP therapy. With this formulation, UVADEX™ (methoxsalen) Sterile Solution is 
introduced ex vivo into the buffy coat bag during the ECP collection process.  
In ECP therapy, when cells have absorbed the drug and are exposed to UVA radiation, 
covalent crosslinks between pyrimidine bases form within the DNA helix, preventing 
replication and leading to apoptotic cell death. Non-nucleated blood components, such 
as red blood cells, are not affected. At the end of the photoactivation cycle, the 
photoactivated cells are then reinfused back to the patient. 
The use of UVADEX™ (methoxsalen) Sterile Solution in conjunction with the 
UVAR® or UVAR XTS®  Photopheresis System is a procedure currently approved and 
marketed for use both in the USA and in several countries outside of the USA as well. 
In summary, UVADEX™ (methoxsalen) Sterile Solution was developed to introduce 
methoxsalen as a liquid into the buffy coat bag during the ECP collection process 
followed by exposure of the cells to UVA light. The rationale for the ex vivo 
introduction of methoxsalen is that it follows consistent, reliable dosing and avoids 
systemic toxicity of the orally administered substance, while still inducing the apoptotic 
effect to the cells. 

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3.1.9 Summary of Clinical Data 
UVADEX™ or oral methoxsalen in conjunction with the UVAR ®, UVAR XTS ®, or 
CELLEX® Continuous Flow System Photopheresis System has been evaluated in 
greater than 25 clinical trials. Completed trials include the following indications:  
 Cutaneous T-Cell Lymphoma 
 Graft-versus-Host Disease 
 Prevention or Treatment of Cardiac or Lung Transplant Rejection 
 Inflammatory bowel Disease-Crohn’s Disease (CD) or Ulcerative Colitis (UC) 
 Rheumatic Diseases-Rheumatoid Arthritis (RA) or Progressive Systemic 
Sclerosis (PSS) 
 Treatment of Chronic Hepatitis C 
3.1.10 Extracorporeal Photopheresis for Acute Graft-Versus-Host Disease 
The study (Acute GvHD-1) was an open-label, randomized trial of ECP in addition to 
corticosteroid therapy compared with corticosteroid therapy alone in the treatment of 
acute GvHD (aGvHD) (Grades II and III, using the modified Seattle Glucksberg 
criteria). The primary objective of the study was to evaluate the incidence of the 
complete response of aGvHD (as defined by no more than Stage I skin disease) to ECP 
treatment. Subjects in this trial who qualified for enrollment received their initial dose 
of corticosteroid therapy (2 mg/kg methylprednisolone equivalent) within 24 hours after 
the diagnosis of Grade II or III aGvHD and, if randomized to the ECP arm, the first 
ECP treatment within 72 hours after the initial diagnosis of Grade II or III GvHD. This 
trial was conducted at 33 study centers in North America, Europe, and Australia. The 
trial was terminated in June of 2007 due to poor enrollment. Eighteen subjects (ECP = 
9; standard therapy = 9) were included in the modified ITT population as of the date of 
discontinuation of the trial. 
Safety 
Five subjects randomized into either the treatment or control arms died during or after 
participation in the study. Four of the 5 subjects who died had severe gut aGvHD as 
manifested by voluminous diarrhea (2-6 liters/day). Two subjects had sepsis with 
multiple organ system failures as terminal events and one additional subject died of 
inanition secondary to severe gut aGvHD. One subject received 1 ECP treatment after 
randomization, discontinued the study, and subsequently died of acute myocardial 
infarction and cardiogenic shock more than 2 months after the single ECP procedure. 
One subject died of septic shock and severe gut aGvHD more than 6 months after being 
randomized into the standard-therapy arm of the study. An independent Data and Safety 
Monitoring Committee for the study reviewed the 5 deaths and concluded that all of the 
deaths were due to the underlying severe aGvHD and not related to the treatment arms 
of the study. 
3.1.11 Extracorporeal Photopheresis for Chronic Graft-Versus-Host Disease 
Extracorporeal Photopheresis (ECP) is an immunomodulatory treatment that involves 
ex vivo collection of mononuclear cells from peripheral blood, exposure to the 

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photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the 
processed cell product into the patient. Although not FDA-approved for the treatment of 
GVHD, ECP may be considered as second-line therapy in patients with acute or chronic 
GVHD and in patients with poor performance status. Its clinical benefits in steroid-
refractory chronic GVHD (SR-cGHVD) have been well documented.17, 18 One 
retrospective analysis showed a 61% overall response rate, with the best responses in 
the skin, oral mucosa, eye, liver, and lung chronic GVHD. In addition, there was 
evidence of a corticosteroid-sparing effect, with a cumulative incidence of 
discontinuation of corticosteroids at 1 year of 22%.21 An additional retrospective 
analysis of 82 patients with SR-chronic GVHD receiving bi-monthly ECP for 6 months 
reported an overall response rate of 79%. In this analysis, Dignan and colleagues 
demonstrated a remarkable 77% and 80% of patients were able to decrease the use of 
immunosuppressive medications and corticosteroids, respectively.22 In addition, two 
systematic reviews of studies evaluating ECP for chronic GVHD revealed pooled 
overall response rates (ORR) of 64% (95% CIs, 47%-79% to 65%-82%).19, 20 Its 
mechanisms of action in chronic GVHD remains unclear, but a number of 
immunomodulatory properties have been proposed, including direct damage to 
pathogenic immune cells via apoptosis induction, impaired antigen presentation and 
antigen-presenting cell activation, increased prevalence of natural killer cells, 
differentiation to and modulation of circulating dendritic cells, and skewing of Th1 
toward Th2 responses. Lastly, ECP is a well-tolerated procedure with rare side effects, 
allowing avoidance of necessary treatment modifications or discontinuation.  
ECP will be initiated at a dose of twice-weekly sessions for 8 weeks. In subjects who 
respond to INCB039110 and ECP, an ECP taper schedule will commence that involves 
once weekly sessions for 8 weeks, then taper to every other week for 8 weeks, and then 
off. 
4 
STUDY DESIGN 
4.1 
Description 
This is an open-label, Phase II trial designed to assess the recommended phase 2 dose 
(RP2D) of itacitinib in combination ECP and efficacy of the combination after 24 weeks of 
therapy. The trial will consist of two parts: Part One will assess the RP2D. For dose-finding 
purposes, the DLT evaluation period will be defined as the time from the first dose of 
itacitinib lead-in (7-day lead-in) to the last day of cycle one combination therapy (cycle one 
day 28). Part Two will further describe and characterize the safety and efficacy of the 
regimen. The RP2D will be determined by a 3+3 dose de-escalation design. Should dose 
level one be deemed intolerable, enrollment will proceed at dose level -1. The RP2D will be 
affirmed according to the rules of the 3+3 dose de-escalation scheme (Section 4.2). Once an 
RP2D has been confirmed, Part 2 will open as an expansion cohort. Safety will be monitored 
during the trial as described in Section 11.3. 
All eligible patients will begin study therapy with approximately a week lead-in of itacitinib 
monotherapy. After completing the itacitinib lead-in, combination treatment will begin in 
28-day cycles. After eight weeks of combination therapy, patients will begin an ECP taper 
and continue on itacitinib for a total of 6 cycles. Patients achieving PR or better may 

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continue on itacitinib for up to 1 year. Patients will remain on study therapy as long as 
treatment discontinuation criteria are not met.  
Prednisone dose (or prednisone equivalent) at ≤ 0.25 mg/kg/d for treatment of GVHD 
progressing or not sufficiently responding to study treatment will be allowed, at the 
discretion of the treating investigator and with approval of the PI, while the participant is on 
study treatment. Addition of prednisone dose (or prednisone equivalent) at ≤ 0.25 mg/kg/d 
will not be considered as failure of the primary endpoint. Prednisone doses (or prednisone 
equivalent) of > 0.25 mg/kg/d but ≤ 0.5mg/kg/d for more than 8 weeks or > 0.5 mg/kg/d 
once will count as a failure of the primary endpoint, but the participant will be allowed to 
remain on the treatment period of the study. If the participant requires any systemic 
immunosuppression besides prednisone (i.e., ibrutinib, ruxolitinib, etc.), the participant will 
be withdrawn from study treatment but remain on study for follow-up. 
4.2 
Part 1: Dose De-Escalation 
A total of 6 to 18 patients may be evaluated in Part 1 depending on the frequency of DLTs 
and the need for dose reductions. A 3+3 dose de-escalation design will be used to determine 
the recommended phase two dose while ensuring the safety and tolerability of the treatment. 
In this trial, the dose determined to be the maximum tolerated dose will be the recommended 
phase two dose and will be utilized in the cohort expansion. The study may test the 
possibility of three dose levels of itacitinib as described in Table 1. 
Table 1: Dose de-escalation Schedule 
 
Itacitinib Dose 
Dose Level 1 (starting dose) 200 mg daily, days 1-28 
Dose Level -1 
100 mg daily, days 1-28 
Dose Level -2 
100 mg every other day, days 1-28 
Eligible subjects will be accrued in cohorts of 3 to 6 subjects per dose level starting at Dose 
Level 1. Three eligible subjects will be enrolled at a time and additional subjects will not be 
accrued until all three subjects have completed the defined DLT evaluation period and 
DSMC approval has been granted. If necessary, dose de-escalation will occur as described in 
Table 2 until DLT stopping rules are met or the lowest dose level is reached. The RP2D will 
be defined as the dose level at which less than one-third of subjects in a cohort experience a 
DLT.  
Table 2: 3+3 Dose de-escalation design 
Number of patients with 
DLT at a given dose level 
De-escalation Rules 
0 out of 3 
Enroll 3 patients at the same dose level 
1 out of 3 
Enter 3 more patients at the same dose level 
 If 1 out of 6 patients experiences a DLT, identify the 
dose level as the RP2D. 

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 If ≥ 2 out of 6 patients experience a DLT, this dose 
level exceeds the MTD. Enroll 3 patients at the next 
lower dose level (if available). 
≥ 2 of 3 
This dose level exceeds the MTD. Enroll 3 patients at the 
next lower dose level (if available). 
In order for a dose level to be declared the RP2D, 6 patients must be treated at that dose 
level with ≤ 1 DLT observed. 
Treatment will initiate at an itacitinib oral dose of 200 mg daily (Cohort 1). If zero or one out 
of three patients have a dose-limiting toxicity (DLT), three additional patients will be accrued 
to Cohort 1. If a DLT occurs in one-third or more of the total cohort, cohort de-escalation 
will be required and three patients will be accrued to Cohort -1. If ≥ two DLTs occur in the 
first three subjects in Cohort -1, three patients will be accrued at the Cohort -2 dose level 
with the same safety parameters. If six patients are ultimately treated at dose Cohort -2 and ≥ 
two DLTs occur, the trial will be stopped and the combination will be deemed unsafe. The 
dose level in which ≤ one patient out of six experiences a DLT (as defined in Section 4.3), in 
accordance to the 3+3 de-escalation rules (as described in Table 2), will be declared the 
RP2D.  
Subjects must have received ≥ 60% of planned INCB039110 (21 doses) and ECP treatments 
(4 treatments) during the DLT observation period to be evaluable for dose tolerability. 
Patients who miss > 40% of planned itacitinib doses or ECP treatments within the DLT 
evaluation period for any reason other than for the management of treatment-related 
toxicities, will not be evaluable and will be replaced.  
If a subject experiences a DLT, the toxicity should be managed per Section 7. The subject 
may remain on study therapy if deriving clinical benefit as assessed by the treating 
investigator.  
Review and approval from the primary medical monitor and DSMC are required prior 
to all cohort expansions and dose escalations. 
4.3 
Dose Limiting Toxicity 
For dose-finding purposes, the DLT evaluation period will be defined as the time from the 
first dose of itacitinib lead-in to the last day of cycle one combination therapy (cycle one day 
28).  The severity of AEs will be graded according to CTCAE v 5.0.  For the purpose of 
dose-finding, any of the following AEs occurring during the DLT period, which are 
attributable (definite, probable, possible) to itacitinib or the combination of itacitinib and 
ECP will be classified as a DLT. 
Table 3: Definition of Dose-Limiting Toxicity 
Hematologic 
 Thrombocytopenia with grade ≥ 3 bleeding (i.e., requires hospitalization, 
transfusion of blood products, or other urgent medical intervention).  

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o 
Transfusion of platelets to meet the requirements of the ECP 
procedure will not be considered a DLT. 
 Platelet count < 10 x 109/L lasting > 3 days. 
 Grade 4 neutropenia lasting > 7 days.  
 Grade 4 neutropenia that does not recover to ≤ Grade 2 in ≤ 7 days after 
interrupting study drug.  
 Grade ≥ 3 febrile neutropenia. 
 Grade ≥ 3 anemia not explained by the underlying disease. 
Non-hematologic 
 Any Grade ≥ 4 non-hematologic toxicity 
 Any Grade 3 non-hematologic toxicity except the following: 
o 
Fatigue lasting < 5 days. 
o 
Any non-Hy's law, liver abnormality that resolves ≤ 72 hours 
o 
Transient (≤ 72 hours) abnormal laboratory values without associated 
clinically significant signs or symptoms.  
o 
Laboratory abnormalities deemed to be not clinically significant by the 
treating investigator. 
o 
Nausea, vomiting, and diarrhea adequately controlled with medical 
therapy within 48 hours.  
o 
Immune-related adverse events that improve to Grade ≤ 1 in < 5 days by 
appropriate care or with corticosteroid therapy. 
o 
An event clearly associated with GVHD, GVHD progression, primary 
disease relapse, a concomitant medication, or comorbidity. 
 Hy’s Law cases: 
o 
ALT or ALT > 3 x upper limit of normal (ULN) or > 3 x ULN and 
doubled from baseline if > ULN at baseline and; 
o 
Total bilirubin > 2 x ULN and; 
o 
Absence of cholestasis and; 
o 
No alternative etiology to explain the abnormalities. 
 Any Grade 3 infection lasting more than 7 days in the absence of the primary 
disease progression. 
General 
 Any adverse reaction unrelated to the primary disease progression that leads to 
dose reduction or withdrawal 
4.4 
Part 2: Dose Expansion 
Upon identification of the Recommended Phase 2 Dose of itacitinib, an expansion cohort will 
open to the enrollment of 40 additional patients for further assessment of regimen safety and 

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efficacy. Enrollment will be conducted in two stages separated by an interim analysis. In the 
first stage of the dose-expansion study, 16 patients will be accrued.  Of those 16 patients, 6 
patients treated at the RP2D will be carried over from Part 1. In recognition of a potential 
accrual pause of at least 24 weeks if all 16 patients are required to complete six months of 
combination therapy, we will permit enrollment of an additional 3 patients after the first 10 
eligible patients in the first stage of the dose-expansion study are enrolled if no more than 5 
of 16 patients have experienced treatment failure (i.e., the addition of secondary systemic 
therapy or disease relapse or death) by the end of week 12 of treatment.  
Once all 10 patients in Part 2 and the six patients treated at the RP2D in Part 1 have met 
treatment failure criteria or completed six months of combination therapy, whichever comes 
first, an interim analysis will be conducted to access treatment efficacy. If ≤ 7 responses (CR 
or PR) in the first 16 enrolled patients are reported, the study will be stopped. Otherwise, the 
next stage of the expansion cohort will open to the enrollment of 30 additional patients.  
4.5 
Number of Patients 
A total of 6 to 18 patients may be evaluated in Part 1 depending on the frequency of DLTs 
and the need for dose reductions. Upon dose confirmation, Part 2 will enroll 40 patients. 
4.6 
Number of Study Centers 
This is a multisite study to be conducted at the Huntsman Cancer Institute at the University of 
Utah, Salt Lake City, Utah. Up to 3 additional sites may be included  
4.7 
Study Duration  
The estimated duration of Part 1 is 6 to 18 months. The total duration of the study will be up 
to 3 years. 
 
 
 

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5 
ELIGIBILITY CRITERIA 
This eligibility checklist is used to determine patient eligibility and filed with the 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) 
5.1.1 _____ Male or female subject aged ≥ 18 years. 
5.1.2 _____ Active, clinically diagnosed, moderate or severe chronic GVHD as defined 
by the NIH Consensus Development Project Criteria (See Appendix 2). 
5.1.3 _____ History of an allogeneic hematopoietic cell transplant with any 
conditioning regimen, donor, or graft source. 
5.1.4 _____ Need for systemic treatment for chronic GVHD as assessed by the treating 
investigator. 
5.1.5 _____ No previous systemic treatment for chronic GVHD. 
Note: Participants may be receiving immunosuppressants for the prophylaxis or 
treatment of acute GVHD, but these medications must have been stable for at 
least 2 weeks prior to the initiation of study therapy. Prednisone dose (or its 
equivalent) should be at doses of ≤ 0.25 mg/kg/d for at least 2 weeks prior to the 
initiation of study therapy. 
Topical or inhaled treatments for chronic GVHD are allowed. Any prior ECP 
treatments for the management of acute GVHD must have occurred > 4 weeks 
prior to the initiation of itacitinib treatment. 
5.1.6 _____ Able to swallow and retain oral medication. 
5.1.7 _____ Life expectancy > 24 weeks. 
5.1.8 _____ Karnofsky performance status ≥ 60  
5.1.9 _____ Evidence of myeloid and platelet engraftment: 
 
Absolute neutrophil count ≥ 1000/mcL 
 
Platelet count ≥ 25,000/mcL 
Note: Use of growth factors and transfusion support is allowed during the study; 
however, growth factors and transfusion support to reach a minimum ANC or 

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platelet count for inclusion are not allowed within the 7 days before the 
screening laboratory assessment. 
5.1.10 _____ Adequate organ function as defined as:  
 Hepatic: 
o Total bilirubin ≤ 2 mg/dL 
o AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN (unless of 
non-hepatic origin). AST/ALT ≤ 5 x ULN is acceptable if 
associated with chronic GVHD.  
 Renal:  
o eGFR ≥ 30 mL/min/1.73 m2 as calculated using the 
Modification of Diet in Renal Disease formula or by the 
Cockcroft-Gault formula:  
 Males: 
(140−𝑎𝑔𝑒)×𝑤𝑒𝑖𝑔ℎ𝑡[𝑘𝑔]
𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [𝑚𝑔
𝑑𝐿]×72 
 Females: (
(140−𝑎𝑔𝑒)×𝑤𝑒𝑖𝑔ℎ𝑡[𝑘𝑔]
𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [𝑚𝑔
𝑑𝐿]×72) × 0.85  
 Coagulation: 
o PT/INR < 1.5 x ULN and PTT (aPTT) < 1.5 x ULN (unless 
abnormalities are unrelated to coagulopathy or bleeding 
disorder). When treated with warfarin or other vitamin K 
antagonist, then INR ≤ 3 x ULN. 
5.1.11 _____ Willingness to avoid pregnancy or father children based on the criteria 
below and as described in Section 5.4.2:    
 Woman of nonchildbearing potential (i.e., surgically sterile with a 
hysterectomy and/or bilateral oophorectomy for at least 3 months OR 
≥ 12 months of amenorrhea and at least 50 years of age). 
 Woman of childbearing potential who has a negative serum pregnancy 
test at screening and negative urinary test before the first dose on Day 
1 and who agrees to take appropriate precautions to avoid pregnancy 
(with at least 99% certainty) from screening through safety follow-up. 
Permitted methods that are at least 99% effective in preventing 
pregnancy should be communicated to the subject and their 
understanding confirmed. 
 Men who agree to take appropriate precautions to avoid fathering 
children (with at least 99% certainty) from screening through safety 
follow-up. Permitted methods that are at least 99% effective in 

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preventing pregnancy should be communicated to the subject and their 
understanding confirmed. 
5.1.12 _____ Able to provide informed consent and willing to sign an approved 
consent form that conforms to federal and institutional guidelines. 
5.2 
Exclusion Criteria 
Yes/No (Response of “yes” = patient ineligible) 
5.2.1 _____ Subjects with score 3 lung GVHD or biopsy-proven bronchiolitis 
obliterans.  
5.2.2 _____ Participants have uncontrolled manifestations of acute GVHD. 
5.2.3 _____ Treatment with any investigational medication within ≤ 30 days or 5 half-
lives, whichever is longer, before the first dose of study drug.  
5.2.4 _____ Patients who have received any previous systemic treatment for chronic 
GVHD, including corticosteroids, prior to Cycle 1, Day 1.  
Note: Prior and concomitant use of Calcineurin-Inhibitors (CNIs) for prevention 
and treatment of acute GVHD, as well as topical/inhaled steroids, is acceptable. 
5.2.5 ______Received prior JAK inhibitor therapy for any indication ≤ 4 weeks prior 
to Cycle 1 Day 1. 
5.2.6 _____ Patients with relapsed or progressive malignant disease or any post-
transplant lymphoproliferative disease. 
5.2.7 _____ Chronic GVHD occurring after a non-scheduled donor lymphocyte 
infusion (DLI) administered for pre-emptive treatment of malignancy 
recurrence. Participants who have received a scheduled DLI as part of their 
transplant procedure and not for management of malignancy relapse are eligible.  
5.2.8 _____ Inability to swallow food or any condition of the upper gastrointestinal 
tract that precludes the administration of oral medications. 
5.2.9 _____ Any contraindication for extracorporeal photopheresis (ECP) per the 
treating investigator’s discretion. 
5.2.10 _____ Subject has a concurrent illness which in the opinion of the investigator 
may interfere with the treatment and evaluation of the subject. 
5.2.11 _____ Pregnant or currently breast-feeding.  
Note: INCB039110 is a JAK1 inhibitor with the potential for serious or life-
threatening birth defects or abortifacient effects.  Because there is an unknown 
but potential risk for adverse events in nursing infants secondary to treatment of 

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the mother with INCB039110, breastfeeding should be discontinued if the 
mother is treated with INCB039110.  These potential risks may also apply to 
other agents used in this study. 
5.2.12 _____ Vaccinated with live, attenuated vaccines within 4 weeks of the first dose 
of study drug and while on trial. 
5.2.13 _____ Use of any prohibited concomitant medications as described in Section 
6.5. A washout period of prohibited medications for a period of at least 5 half-
lives or as clinically indicated should occur prior to the start of treatment. 
5.2.14 _____ Inadequate recovery from toxicity and/or complications from major 
surgery before starting therapy. 
5.2.15 _____ Unwillingness to be transfused with blood components during the study. 
5.2.16 _____ History of other malignancy (not including the underlying malignancy that 
was the indication for the transplant), with the following exceptions: 
 Malignancy treated with curative intent and with no evidence of active 
disease present for more than 3 years prior to Screening and felt to be 
at low risk for recurrence by the treating physician. 
 Adequately treated non-melanomatous skin cancer or lentigo maligna 
melanoma without current evidence of disease. 
 Adequately treated cervical carcinoma in situ without current evidence 
of disease. 
5.2.17 _____ The subject has uncontrolled, significant intercurrent or recent illness 
including, but not limited to, the following conditions: 
 Clinically significant or uncontrolled cardiac disease, including 
unstable angina, acute myocardial infarction within 6 months of 
enrollment, NYHA Class III or IV congestive heart failure, circulatory 
collapse requiring vasopressor or inotropic support, or an arrhythmia 
that requires therapy. 
 A clinically significant respiratory disease that requires mechanical 
ventilation support or ≥ 50% oxygen. 
 Any uncontrolled active systemic infection or active infection 
requiring systemic treatment that was ongoing ≤ 7 days before 
screening. Subjects with acute infections requiring treatment should 
delay screening/enrollment until the course of therapy has been 
completed and the event is considered resolved. Prophylactic 
antibiotics will be permitted. 
 Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/ 
veno-occlusive disease of the liver (defined as persistent total bilirubin 

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> 2 mg/dL, or abnormalities not attributable to GVHD and ongoing 
organ dysfunction). 
5.2.18 _____ History of thromboembolic event within 1 month before study 
registration. 
5.2.19 _____ HIV-infected patients on effective antiretroviral therapy with an 
undetectable viral load within 6 months are eligible for this trial. 
5.2.20 _____ Active HBV or HCV infection that requires treatment, or at risk for HBV 
reactivation (i.e., positive HBsAg). Participants with negative HBsAg and 
positive total HBc antibody may be included if HBV DNA is undetectable at the 
time of screening. Participants who are positive for HCV antibodies are eligible 
only if PCR is negative for HCV RNA. Participants whose immune status is 
unknown or uncertain must have results confirming immune status before 
enrollment. Serology results performed less than or equal to 6 months prior to 
the first planned dose of itacitinib are acceptable for determining eligibility.  
5.2.21 _____ Known prior severe hypersensitivity to investigational product or any 
component in its formulations, including known severe hypersensitivity reactions 
to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3). 
5.2.22 _____ Any condition that would, in the investigator’s judgment, interfere with 
full participation in the study, including administration of study drug/treatment 
and attending required study visits; pose a significant risk to the participant; or 
interfere with the interpretation of study data. 
5.2.23 _____ Unable to understand the purpose and risks of the study and to provide a 
signed and dated informed consent form (ICF) and authorization to use protected 
health information (in accordance with national and local subject privacy 
regulations) per the investigator’s assessment. 
 
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. 
5.4 
Lifestyle Considerations 
5.4.1 Meals and Dietary Restrictions 
Participants should be instructed to refrain from the consumption of pomegranates, 
pomegranate juice, grapefruits, grapefruit juice, or Seville oranges as these are known to 
inhibit cytochrome CYP3A4 enzymes and may increase exposure to itacitinib. 
5.4.2 Contraception 
The effects of INCB039110 on the developing human fetus are unknown. For this 
reason and because JAK inhibitor agents are known to be teratogenic, women of 
childbearing potential and men with partners of childbearing potential must agree to use 
highly effective contraception from the start of study therapy, for the duration of study 
therapy, and for 30 days after the last dose of INCB039110. Should a woman become 
pregnant or suspect she is pregnant while she or her partner is participating in this study, 
she should inform the treating investigator immediately. Men treated or enrolled on this 
protocol must also agree to the use of highly effective contraception prior to the study, 
for the duration of study participation, and 30 days after completion of INCB039110 
administration. 
Acceptable highly effective contraceptive methods include: 
 Bilateral tubal occlusion 
 Vasectomized partner 
 Intra-uterine devise (IUD) or hormone-releasing system (IUS) 
 Any hormonal (estrogen combined with progesterone or progesterone alone) 
contraception associated with inhibition of ovulation: implanted, oral, 
intravaginal, transdermal, or injectable. 
 The combination of two compatible barrier methods with or without spermicide 
(i.e., diaphragm, sponge, or male or female condoms). 
 Abstinence from heterosexual intercourse.  
6 
TREATMENT PLAN 
6.1 
Administration Schedule 
Treatment will be administered on an outpatient basis. Eligible patients will self-administer 
itacitinib every morning regardless of food. At the end of 8 weeks of combination therapy, 
patients will start a standard ECP taper schedule and itacitinib will be continued at the 
assigned dose level. Patients achieving PR or better after 6 cycles of itacitinib may continue 
treatment with itacitinib for up to 1 year. Thereafter, itacitinib may be tapered at the treating 
investigator’s discretion as described below.  

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6.1.1 ECP Taper 
ECP will be given at a frequency of twice weekly for 8 weeks followed by a standard 
taper schedule as detailed below. Local institutional guidelines should be followed for 
the safe administration of ECP. Once a taper has initiated, investigators may consider 
increasing the frequency of ECP by one level if there is concern for GVHD progression 
and if prednisone (or prednisone equivalent) is not administered. This should be 
discussed with the PI first. 
Table 4: Recommended ECP Schedule 
Week 
ECP Schedule 
1-8 (Start of therapy) 
Twice weekly  
9-16 
Once weekly 
17-24 
Once every other week 
25+ until physician discretion 
Once monthly 
During the taper, immune suppression will continue as described below.  
6.1.2 Itacitinib Taper 
If a participant has achieved CR or PR after six cycles of therapy, investigators may 
continue itacitinib for up to 1 year. Thereafter, investigators may begin to taper the dose 
of itacitinib by 1 dose level. Subsequent tapering may occur within 28 to 56 days after 
the initial taper, as appropriate. Participants who are still receiving CNIs, sirolimus, or 
corticosteroids for GVHD treatment at this time may continue to do so at the treating 
investigator's discretion. If GVHD signs/symptoms worsen during the taper of itacitinib, 
the dose may be escalated by 1 dose level. 
6.1.3 Prednisone Taper 
If a participant has been initiated on prednisone dose (or its equivalent) during treatment 
with ECP and Itacitinib, investigators may begin to taper the corticosteroid dose as per 
their institutional guidelines or at the treating investigator’s discretion. Participant’s 
prednisone dose (or its equivalent) should be at < 0.25mg/kg/d after 8 weeks from 
initiation of corticosteroid. If this is not achieved, the participant will be considered a 
treatment failure but may remain on study treatment and follow-up period.  
6.1.4 Immune Suppression with Calcineurin Inhibitors or Sirolimus 
Tapering of standard immune suppression (tacrolimus, cyclosporin, sirolimus) used for 
prophylaxis or treatment of acute GVHD may be tapered at the physician’s discretion. If 
immune suppression is at treatment doses for cGVHD, tapering of immune suppression 
should only occur after the subject has achieved a treatment response and after 
following the withdrawal of prednisone (if applicable).  
 
  CNIs and/or sirolimus may be reduced per institutional practices. 
 

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6.2 
Itacitinib 
6.2.1 How Supplied, Stored, Packaged and Labeled 
Incyte will supply itacitinib as 100 mg sustained-release tablets. These tablets contain 
the active ingredients, microcrystalline cellulose, lactose monohydrate, pregelatinized 
starch, hydroxypropyl cellulose, sodium starch glycolate, and magnesium stearate. 
Investigationally labeled bottles will be packaged in high-density polyethylene bottles 
with child-resistant closures including an induction seal liner. They will be dispensed by 
appropriately trained and delegated personnel to patients. If dose modifications are 
necessary, patients will be dispensed the appropriate number of investigationally 
labeled bottles.  
Store at ambient conditions 15°C to 30°C (59°F to 86°F). Protect from moisture and 
light. Do not place the medication in pillboxes.  
6.2.2 Preparation and Administration 
Investigational study medication will be prepared and dispensed by properly trained and 
delegated individuals. Patients will self-administer itacitinib by mouth regardless of 
food once daily. Doses should be taken every morning (± 8 hours) and recorded on the 
patient's dosing diary. Patients should be instructed to hold their dose until after their 
blood is drawn on days that they will be seen in the clinic. Doses missed outside of the 
dosing window should not be made up, but rather, patients should be instructed to take 
their next dose at their regularly scheduled time.  
6.2.3 Accountability and Compliance 
A patient dosing diary will be provided to the patients to aid in patient compliance with 
the dosing instructions. The diary will be maintained by the patient to include missed or 
changed itacitinib doses. The time of each dose administration and the number of tablets 
taken each day will be recorded in the dosing diary. Patients will be required to return 
the completed patient dosing diary on Day 1 of every cycle for timely review by site 
personnel and discussion of missed doses and/or compliance issues. 
Patients will also be required to return all unused itacitinib tablets at the end of every 
cycle. The number of tablets returned by the patient will be counted, documented, and 
recorded by site personnel and reconciled with the patient’s dosing diary to support the 
itacitinib accountability process. Excess or unused study drug returned to the 
investigative site will be destroyed in accordance with GCP after drug accountability 
has been performed.  
Treatment compliance (reported as a percent) will be defined as the number of tablets or 
capsules taken during the study divided by the expected number of tablets or capsules, 
multiplied by 100%.  

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6.3 
Extracorporeal Photopheresis 
All ECP treatments will be prepared and administered according to local institutional 
practices and guidelines. All doses will be administered at the investigational site by well-
trained medical staff. The start and stop times of the infusions, along with the total volume 
administered, will be recorded in the patients’ medical records. Additionally, the start and 
stop times of any interruptions to infusions and/or changes in the rate of infusion will also 
need to be recorded in the patients’ medical records. Any reason that treatment is missed or 
altered should be clearly documented in the patient’s research chart. 
Due to the risk of thromboembolic events, clinic staff involved in ECP procedures will be 
advised to be alert for symptoms of pulmonary embolism (PE) and deep vein 
thromboembolism (DVT) during and following ECP therapy. Symptoms may include 
shortness of breath, cough, chest pain, fever, cyanosis, leg pain with or without swelling, 
dizziness, and irregular heartbeat. Patients will be advised upon discharge that should they 
develop these symptoms to immediately seek urgent medical attention at the nearest 
emergency room. Treating investigators should consider the necessity of anticoagulation and 
heparin dose adjustment according to device labeling and individual patient need.  
6.4 
Concomitant Medications and Therapies 
All concomitant medications and treatments utilized 28 days prior to Cycle 1 Day 1 and 30 
days after the last dose of study medication must be recorded in the patient’s Case Report 
Form (CRF). The subject needs to notify the investigational site about any new medications 
he/she takes after the start of the study drug. All medications (other than study drug) and 
significant nondrug therapies (including physical therapy and blood transfusions) 
administered after the subject starts treatment with study drug must be listed on the 
Concomitant Medications/Significant Nondrug Therapies after the start of the study drug. 
Since there is a potential for interaction of itacitinib with other concomitantly administered 
drugs through the cytochrome P450 system, the case report form must capture the concurrent 
use of all other drugs, over-the-counter medications, or alternative therapies.  The Principal 
Investigator should be alerted if the patient is taking any agent known to affect or with the 
potential for drug interactions. The study team should check a frequently updated medical 
reference for a list of drugs to avoid or minimize the use of.   
 
6.5 
Ancillary Therapy and Supportive Care 
Topical corticosteroid therapy and regimens to treat or prevent bronchiolitis obliterans (e.g., 
inhaled corticosteroids) may be continued per institutional guidelines.  
Other supportive medications in accordance with standard clinical practice (such as for 
emesis, diarrhea, osteoporosis etc.) are permitted. Use of neutrophil growth factors 
(filgrastim and pegfilgrastim), red blood cell growth factors (erythropoietin) or TPO receptor 
agonists (romiplostim, eltrombopag) is permitted per institutional policy for Part 2 
participants only. Transfusions may be given in accordance with institutional policy.  
 

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6.6 
Prophylaxis for Infectious Diseases 
6.6.1 Pneumocystis Pneumonia Prophylaxis 
All subjects receiving study treatment with INCB039110 are required to receive a standard 
PJP prophylaxis regimen determined by the investigator. Examples of standard PJP 
prophylaxis therapies for this population include trimethoprim-sulfamethoxazole, 
atovaquone, dapsone with or without pyrimethamine, and pentamidine (NCCN 2014). 
Subjects with a previous or suspected allergy to sulfonamide antibiotics must receive 
prophylaxis with atovaquone (Mepron) or pentamidine. Prophylaxis should be given while 
subjects are receiving study treatment and continue at a minimum an additional 60 days 
after the last dose of itacitinib or through the taper of all immunosuppression. 
6.6.2 Prophylaxis for Encapsulated Bacteria and Fungal Infections 
Antibiotic and antifungal prophylaxis should be given per institutional standards while 
subjects are receiving study treatment. Concomitant use of strong CYP3A4 inhibitors 
such as itraconazole, voriconazole, and clarithromycin are restricted during study 
therapy. If antifungal therapy is necessary, use of an agent with less CYP3A4 inhibition 
is recommended, such as posaconazole, isavuconazole, or fluconazole. Careful 
monitoring of hematology parameters and clinical signs and symptoms of itacitinib-
related adverse reactions is recommended upon initiation of a CYP3A4 inhibitor.  
6.6.3 Restricted Therapy 
The following medications have restrictions on use during the treatment period of the 
study. 
 Use of potent CYP3A4 inhibitors, such as itraconazole, voriconazole, 
mibefradil, and clarithromycin. If treatment with one of these drugs is 
required, a dose reduction of itacitinib to 100 mg daily is recommended. 
o Based on the low overall bioavailability of topical ketoconazole, there 
are no restrictions on topical ketoconazole in the study.  
o No dose adjustment is recommended for concomitant administration of 
other CYP3A4 inhibitors.  
 
P-glycoprotein substrates of clinical relevance should be used with caution.  
 
If concomitant administration of an anticoagulant/antiplatelet medication is 
indicated, then caution and enhanced monitoring are required. The presence and 
severity of thrombocytopenia should be a factor in the choice of anticoagulant 
and dose. The use of aspirin at doses > 81 mg per day should be avoided. 
Acetaminophen and nonsteroidal anti-inflammatory agents (NSAIDs, e.g., 
ibuprofen) may be used at over-the-counter doses. Due to the risk of liver injury 
with the use of high doses of acetaminophen, subjects should be advised to stay 
within the recommended daily dose of acetaminophen. 
6.6.4 Prohibited Therapy 
The following medications are prohibited during the study unless stated otherwise. 

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 Any investigational medication other than the study drug is prohibited. Use of 
such medications within 30 days or 5 half-lives, whichever is longer, before the 
first dose of study drug and during the study through the safety follow-up visit is 
prohibited. Therapies which would typically be prohibited may be administered if 
necessary to preserve the health or safety of a participant (e.g. vaccines or 
medical products for prevention or treatment of COVID-19).  Principal 
Investigator and Medical Monitor should be informed of any administration. 
Administration of these therapies should be avoided immediately prior to ECP 
 Addition of any other new systemic medications/therapies other than 
extracorporeal photopheresis to treat chronic GVHD (e.g., calcineurin inhibitors, 
sirolimus, rituximab, imatinib, etanercept, anti-thymocyte globulin, bortezomib, 
methotrexate, mycophenolate mofetil, other cytotoxics or immune modulators, 
other JAK inhibitors, or any investigational agent) is not permitted at any time 
from screening to the time that INCB039110 therapy is permanently 
discontinued.  
At enrollment, subjects may be receiving other immunosuppressants (e.g., 
calcineurin inhibitors, sirolimus) for the prophylaxis of GVHD or treatment of 
acute GHVD. The doses of these medications must have been stable for at 
least 2 weeks prior to Screening. Adjustments (increases or decreases) to 
existing immunosuppression are allowed if these adjustments are necessary to 
maintain a therapeutic drug level. Tapering of immunosuppression is 
permitted at the provider’s discretion and should follow per institutional 
practice.  
If cGVHD develops or worsens during the tapering of existing 
immunosuppression (e.g., calcineurin inhibitors, sirolimus) for prophylaxis or 
treatment of aGVHD, the dose of the immunosuppressant may be increased 
again and will not be considered a treatment failure. A short course of low-
dose prednisone (or equivalent) ≤ 0.5 mg/kg/d may be considered. Tapering of 
immunosuppression in this setting should occur after the subject has achieved 
a treatment response and has withdrawn prednisone (if applicable).  
Use of immunosuppression for reasons other than treatment for cGVHD 
should be discussed with the medical monitor. 
 
The use of systemic corticosteroid doses of prednisone (or equivalent) > 0.5 
mg/kg/day for treatment of acute or chronic GVHD.  
o If a subject requires corticosteroid doses of prednisone (or equivalent) > 
0.25 mg/kg/day for the underlying disease or a comorbid condition 
during study participation, then continuation in the study will be 
considered on an individual basis by the sponsor and the investigator. 
 Subjects receiving itacitinib should avoid consuming pomegranates, 
pomegranate juice, grapefruits, grapefruit juice, or Seville oranges, all of which 
are known to inhibit cytochrome CYP3A enzymes and may increase the 
exposure to itacitinib. 

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 Coadministration with potent CYP3A4 inducers. The FDA website provides a 
current list of potent CYP3A4 inducers. 
 The use of TPO receptor agonists (romiplostim, eltrombopag) is not permitted 
from screening to the safety follow-up visit (within the DLT period).  
 The use of erythropoietin is not permitted from screening to the safety follow-
up visit (within the DLT period).  
 Live attenuated vaccines within 28 days prior to the first dose of study 
treatment and while participating in the study are prohibited. Examples of live 
vaccines include, but are not limited to: measles, mumps, rubella, 
chickenpox/zoster, yellow fever, rabies, BCG, and typhoid (oral) vaccine. 
Seasonal influenza vaccines for injection are generally killed virus vaccines 
and are allowed; however, intranasal influenza vaccines (e.g., Flu Mist®) are 
live-attenuated vaccines and are not allowed.  
 No surgery (except biopsy), investigational treatment, immunotherapy, or 
additional chemotherapy is allowed during the course of this study. 
6.7 
Duration of Therapy 
In the absence of treatment delays due to an adverse event(s), treatment may continue for 12 
cycles (i.e., 12 months) or until criteria for treatment discontinuation are met. 
6.7.1 Criteria for discontinuation of treatment (“off-treatment”) 
Patients may withdraw from treatment or the study overall at any time at their own 
request, or they may be withdrawn at the discretion of the Investigator for safety, 
behavioral reasons, or the inability of the patient to comply with the protocol-required 
schedule of study visits or procedures. In addition to the drug-specific discontinuation 
criteria listed in Section 6.6, 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 own request or at the request 
of his legally acceptable representative. 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. 
 Treatment failure as defined as: 
o Need for additional systemic therapy for GVHD. 
 If a patient has been tapered off a calcineurin inhibitor or 
sirolimus used for GVHD prophylaxis at the time of diagnosis 
of moderate-severe chronic GVHD, reinstitution of the drug 
will not be considered a failure.  
 Prednisone dose (or prednisone equivalent) used at > 0.25 
mg/kg/d for more than 8 weeks or > 0.5 mg/kg/d once will 
count as a treatment failure, but the participant will be allowed 

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to remain on the study treatment if deemed to be clinically 
benefiting by the treating investigator.  
 If the participant requires any systemic immunosuppression 
besides prednisone (i.e., ibrutinib, ruxolitinib, etc.), the 
participant will be withdrawn from study treatment but remain 
on study for follow-up. 
o Relapse of primary hematologic disease. 
o Death 
 Clinical deterioration that, in the opinion of the investigator, increases the risk to 
the patient. 
 AEs or intercurrent illness that, in the opinion of the investigator, warrants the 
subject’s withdrawal from study treatment. 
 Significant noncompliance (defined as missing ≥ 40% of required study 
medication) with the protocol schedule or treatment administration in the opinion 
of the investigator. 
 An intercurrent illness that prevents further administration of treatment. 
 General or specific changes in the patient's condition render the patient 
unacceptable for further treatment in the judgment of the investigator. 
 Pregnancy. 
 Termination of the study by the sponsor. 
 The drug manufacturer can no longer provide the study agent. 
 Death. 
The reason(s) for protocol therapy discontinuation, the reason(s) for study removal, and 
the corresponding dates must be documented in the Case Report Form (CRF). 
6.7.2 Criteria for discontinuation of study (“off study”) 
Subjects will be taken off study for the following: 
 Completed study follow-up period 
 Participant requests to be withdrawn from the study 
 If, in the investigator's opinion, the continuation of the trial would be harmful to the 
subject's well-being. 
 Development of intercurrent illness or situation which would, in the judgment of 
the investigator, significantly affect assessments of clinical status and trial 
endpoints. 
 The subject is lost to follow-up.  
 Death. 

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 Screen failure. 
7 
TOXICITIES AND DOSE MODIFICATION 
Every effort should be made to administer the investigational product at the planned dose and 
schedule. In the event of study treatment toxicity, dosing may be interrupted, delayed, and/or 
reduced, as described in Section 7.4. In the event of multiple toxicities, treatment/dose 
modifications should be based on the worst toxicity observed (CTCAE v5.0) and/or the most 
conservative recommendation for any given toxicity. Patients are to be instructed to notify 
Investigators at the first occurrence of any adverse symptom. 
All dose modifications must be clearly documented in the patient's medical chart and in the CRF.  
Appropriate follow-up assessments should be done until adequate recovery occurs as assessed by 
the Investigator. 
7.1 
Dose Modifications during the DLT period 
Dose reductions of itacitinib are not allowed during the DLT period unless a DLT has been 
confirmed for a specific patient. Dose reduction due to a drug-drug interaction (i.e. potent 
CYP3A4 inhibitors) will not be considered a DL, but these subjects will not be considered 
evaluable for DLT and will be replaced. If a subject experiences toxicity that meets DLT 
criteria during the DLT observation window, the patient should be taken off treatment. If the 
treating investigator feels that the patient is deriving clinical benefit, the patient may remain 
on study therapy only after discussion with and approval from the Principal Investigator.  
After completion of the DLT observation period, dose modifications are allowed for patients 
who do not tolerate the protocol-specified itacitinib dosing to allow the patient to continue the 
study treatment. Dose modification guidelines are described below. 
7.2 
Dose Interruptions 
Dose interruptions for study treatment-related AEs are allowed as per the dose modification 
recommendations. Doses of any investigational product that were not administered due to 
toxicity will not be replaced within the same cycle. In addition to dose interruption, the need 
for a dose reduction at the time of treatment resumption should also be considered based on 
the dose modifications recommendations. Treatment with itacitinib may be delayed up to 2 
weeks (14 days) to allow for the resolution of toxicity. Participants may resume treatment if 
no medical condition or other circumstance exists that, in the opinion of the investigator, 
would make the participant unsuitable for further participation in the study.  The treating 
investigator should contact the Principal Investigator to discuss the case of any participant 
whose treatment has been delayed for more than 14 days before restarting treatment with 
itacitinib.  
7.3 
Dose Reductions 
Following dosing interruption due to treatment-related toxicity, the study drug may need to 
be resumed at a reduced dose as per the dose modification recommendations. Dose reduction 
should proceed by decreasing the administered dose by one dose level per Table 5. 

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Once the study treatment has been reduced for a given patient, all subsequent cycles should 
be administered at that dose level. Intra-patient dose re-escalation is not allowed. 
 
Table 5: Itacitinib Dose Levels 
Dose Level 
Itacitinib 
1 
200 mg oral daily, Days 1-28 each cycle 
-1 
100 mg oral daily, Days 1-28 each cycle 
-2 
100 mg oral every other day, Days 1-28 each cycle 
 
7.4 
Guidelines for Management of Adverse Events 
After completion of the DLT period, patients experiencing adverse events attributed to 
itacitinib may undergo dose modifications for toxicity management. Since participants may 
enter the study with extensive pretreatment conditions and/or compromised bone marrow 
function, dose reduction recommendations provided in Table 6 are provided as guidelines.  
Individual decisions regarding dose modifications should be made using clinical judgment 
and an individual benefit/risk assessment taking into account relatedness of the AE to the 
study treatment and the participant's underlying condition. Adverse events that have a clear 
alternative explanation, or transient (≤ 72 hours) abnormal laboratory values without 
associated clinically significant signs or symptoms, may be exempt from dose modification 
rules. 
Table 6: Adverse Event Management Guidelines  
ADVERSE EVENT 
MANAGEMENT 
Transaminitis 
AST and/or ALT > 3.0 × ULN if 
normal ALT/AST at baseline. 
1. Interrupt for up to 14 days until the toxicity has 
resolved to ≤ Grade 1.   
2. Restart at the previous dose.  If assessed as related to 
itacitinib, restart at the next lower dose and monitor as 
clinically indicated. NOTE:  In participants with GVHD-
related chemistry elevations at baseline, contact the 
sponsor to discuss clinical management and possible dose 
reductions.  
Total bilirubin elevations that 
occur in the presence of GVHD 
response that cannot be attributed 
to new liver GVHD or 
concomitant therapy.  
Total bilirubin 3.0-5.0 × ULN:  
 Repeat assessment within 7 days.  If elevation persists: 
o Reduce dose by 1 level until bilirubin ≤ 1.5 × 
ULN.  

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ADVERSE EVENT 
MANAGEMENT 
 
o Resume the previous dose if resolved in 14 
days; if > 14 days, maintain a reduced dose.  
Total bilirubin > 5.0-10.0 × ULN:  
 Repeat assessment within 7 days.  If elevation persists:  
o Interrupt until bilirubin ≤ 1.5 × ULN.  
o Monitor LFTs weekly or more frequently as 
appropriate.  
o Resume the previous dose if resolved in 14 
days; if > 14 days, resume at reduced dose.  
Total bilirubin > 10.0 × ULN:  
 Repeat assessment within 7 days.  If elevation persists: 
o Interrupt until bilirubin ≤ 1.5 × ULN.  
o Resume at reduced dose if resolved in 14 days; 
if > 14 days, discontinue treatment and monitor 
as appropriate. 
 
Total bilirubin elevations that 
occur in participants with score ≥ 
1 liver GVHD that cannot be 
attributed to worsening liver 
GVHD or concomitant therapy. 
 
Total bilirubin > 3.0 × ULN:   
 Repeat assessment within 7 days.  If elevation persists: 
o Reduce dose by 1 dose level.  
o Resume previous dose if bilirubin ≤ 3.0 × 
ULN. 
 
Neutropenia 
ANC < 0.5 × 109/L, suspected as 
unrelated to study drug (e.g., 
GVHD, active cytomegalovirus 
viremia). 
 Reduce dose by 1 dose level. 
 Monitor ANC count as clinically indicated.  
 Resume the previous dose if the ANC count is ≥ 0.5 × 
109/L for more than 7 days.  
ANC < 0.5 × 109/L, suspected as 
related to study drug. 
 Interrupt for up to 14 days.  
 Monitor ANC count as clinically indicated.  
 Resume at a reduced dose if the ANC count is ≥ 0.5 × 
109/L for more than 7 days.  If the ANC count remains 
at ≥ 0.5 × 109/L for more than 7 days after resuming 
treatment at a lower dose, the previous dose may be 
resumed.  
Thrombocytopenia 
Platelet count < 10 × 109/L or 
platelet count has decreased by ≥ 
50% from baseline, suspected as 
unrelated to study drug. 
 Reduce dose by 1 dose level.  
 Monitor platelet count as clinically indicated.  

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ADVERSE EVENT 
MANAGEMENT 
 Resume at previous dose if platelet count returns to ≥ 
20 × 109/L or recovers to within 75% of the baseline 
value for more than 7 days.  
Platelet count < 10 × 109/L or 
platelet count has decreased by ≥ 
50% from baseline, suspected as 
related to study drug. 
 Interrupt for up to 14 days.  
 Monitor platelet count as clinically indicated.  
 Resume at a reduced dose if platelet count returns to ≥ 
20 × 109/L for more than 7 days or recovers to within 
75% of the baseline value.  If the platelet count 
remains stable for an additional 7 days, the previous 
dose may be resumed.  
Other Non-hematologic toxicities 
Any Grade 1 or Grade 2 toxicity.  Continue treatment and manage the toxicity.  
 Monitor as clinically indicated. 
Any Grade 3 toxicity, not 
manageable by supportive care. 
 Interrupt up to 14 days until toxicity resolves to ≤ 
Grade 1.  
 Restart at the same dose; if assessed as related to 
itacitinib, restart at next lower dose and monitor as 
clinically indicated. 
Any recurrent Grade 3 toxicity at 
100 mg QOD dose. 
Discontinue study treatment; follow-up per Protocol.  
Grade 4 
Discontinue study treatment; follow-up per Protocol.  
7.5 
Supportive Care 
All treatments that the investigator considers necessary for a subject's welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care. All concomitant medication will be recorded on the eCRF, including all 
prescription, over-the-counter, herbal supplements, and IV medications and fluids. If changes 
occur during the study period, documentation of drug dosage, frequency, route, and date may 
also be included on the eCRF 
The subject needs to notify the investigational site about any new medications he/she takes after 
the start of the study drug. All medications (other than study drug) and significant nondrug 
therapies (including physical therapy and blood transfusions) administered after the subject starts 
treatment with study drug must be listed on the Concomitant Medications/Significant Nondrug 
Therapies After Start of Study Drug eCRF. 
The use of prophylactic growth factors are not permitted during Part 1. However, during Part 2, 
neutrophil growth factors may be used at the treating investigator’s discretion based on American 
Society of Clinical Oncology guidelines for the use of WBC growth factors (Smith et al., 2006). 
The use of erythropoietin will be in strict compliance with FDA recommendations in the 
current prescribing information. Bisphosphonates are allowed while subjects are receiving study 

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treatment. The use of intravenous immunoglobulin is allowed while subjects are receiving study 
treatment as per institutional guidelines. 
Flu-like symptoms (fever, headache, myalgias, arthralgias) may be treated with aspirin, 
Tylenol, NSAIDs, or antihistamines as clinically indicated per the investigators’ judgment.  
Diarrhea may be treated initially with loperamide as clinically indicated, with additional 
interventions per the investigators’ judgment. 
Nausea and vomiting may be treated with 5HT3 receptor antagonists as clinically 
indicated, with additional interventions per the investigators’ judgment. 
Hematologic support with granulocyte-colony stimulating factor and/or transfusions of 
packed red blood cells and/or platelets may be given as clinically indicated after completion 
of the DLT period, per ASCO, NCCN or institutional guidelines. It is prohibited during the 
first 28 days of the study. The use of erythropoietin, romiplastin, and eltrombopag will be 
in strict compliance with FDA recommendations in the current prescribing information. 
Itacitinib has the potential to cause WBC margination (i.e., a transient decrease in absolute 
neutrophil count [ANC]), assessment of hematology parameters should be performed 
before study drug administration at all applicable study visits. 
8 
SCHEDULE OF EVENTS 
The Schedule of Events table provides an overview of the protocol visits and procedures.  Refer 
to the Study Procedures section of the protocol for detailed information on each assessment 
required for compliance with the protocol. The Investigator may schedule visits (unplanned 
visits) in addition to those listed in the Schedule of Events table in order to conduct evaluations 
or assessments required to protect the wellbeing of the patient. This Schedule of Events will be 
followed for the entire study. 
 

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Table 7: Schedule of Events 
Protocol Activities 
Screening1 
On-Treatment Period: One Cycle = 28 days 
Off Treatment Period 
Lead-
In2 
Cycle 1 
Cycle 
2 & 3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycles 
8 – 12 
PD 
Visit3 
EOT4 
Follow-Up5 
Week 
 
 
1 
3 
5 & 9 
13 
17 
21 
25 
29 – 
45 
30 days from last 
dose 
Every 12 
weeks 
Day of the Cycle 
(Visit Window) 
(-28 days) 
-10 
to -5 
days 
16 
15 
(+ 3 
days) 
1 
(± 5 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
 days) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics7 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Registration 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Assessments 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Karnofsky Score8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pulmonary Function 
Test9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry9 
X 
 
 
 
 
X 
 
 
X 
X8 
X 
X 
 
2-min walk test10 
X 
 
X 
 
X 
X 
 
X 
 
X 
X 
X 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Adverse event 
collection11 
 
X 
 
Concomitant 
medications 
collection 
 
X 
 
Laboratory Studies 
Hematology12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Coagulation14 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid panel15 
X 
 
 
 
 
X 
 
 
X 
X 
X 
X 
 
Pregnancy Test16 
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Activities 
Screening1 
On-Treatment Period: One Cycle = 28 days 
Off Treatment Period 
Lead-
In2 
Cycle 1 
Cycle 
2 & 3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycles 
8 – 12 
PD 
Visit3 
EOT4 
Follow-Up5 
Week 
 
 
1 
3 
5 & 9 
13 
17 
21 
25 
29 – 
45 
30 days from last 
dose 
Every 12 
weeks 
Day of the Cycle 
(Visit Window) 
(-28 days) 
-10 
to -5 
days 
16 
15 
(+ 3 
days) 
1 
(± 5 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
 days) 
HIV and Hepatitis 
serologies17 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Quantitative serum 
immunoglobulins18 
X 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Absolute CD4 
Count19 
X 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Infection 
monitoring20 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Disease Assessments 
Chronic GVHD 
assessment 
X 
 
X21 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Graft failure/ 
chimerisms22  
X 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
Malignancy relapse 
assessment23 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Survival Status 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient Reported Outcomes24 
Lee chronic GVHD 
Symptom Scale 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
QOL-SF-36v.2 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
AM-PAC Basic 
Mobility Outpatient 
Routine Short Form 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Study Therapy 
ECP 25 
 
 
X 
 
 
 
 
 
Itacitinib26 
 
X 
 
 
 
Immune 
suppression27 
X 
 
 
Documentation of 
systemic 
corticosteroid dose 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 

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Protocol Activities 
Screening1 
On-Treatment Period: One Cycle = 28 days 
Off Treatment Period 
Lead-
In2 
Cycle 1 
Cycle 
2 & 3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycles 
8 – 12 
PD 
Visit3 
EOT4 
Follow-Up5 
Week 
 
 
1 
3 
5 & 9 
13 
17 
21 
25 
29 – 
45 
30 days from last 
dose 
Every 12 
weeks 
Day of the Cycle 
(Visit Window) 
(-28 days) 
-10 
to -5 
days 
16 
15 
(+ 3 
days) 
1 
(± 5 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
days) 
1 
(± 7 
 days) 
Correlative Studies 
Blood for 
correlative studies28 
X 
 
X29 
 
 
 
 
 
X 
 
X 
X30 
 
 

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1 Screening procedures must be completed ≤ 28 days prior to the start of itacitinib lead-in.  
2 Itacitinib dosing will begin 5 to 10 days prior to C1D1. 
3 Progressive Disease visit should occur at the time that disease progression is found (+7 days). PFT’s should be completed within 4 weeks of the PD visit. 
4 End of Treatment visit should occur 30 days (± 7 days) after the last treatment dose of itacitinib. 
5 Patients will be followed for survival and disease status after coming off treatment. These visits should occur every 3 months for up to 12 months after coming 
off-treatment. 
6 All procedures must be completed prior to the start of study therapy. 
7 Demographic information will include the following: change in residence, annual income, insurance type, and employment status. 
8 See Appendix 1: Karnofsky Performance Status. 
9 Pulmonary function tests (PFT) with spirometry are required at screening. Only Spirometry is required at C4D1, C7D1, C10D1, and at the EOT or PD visit. 
PFTs and/or spirometry may be conducted ≤ 7 days prior to the scheduled day one visit to allow for timely review of results. 
10 Patients will be instructed to walk without assistance for 2 minutes and the distance traveled in feet will be recorded in the eCRF. This will occur at C1D1, 
C2D1, C3D1, C6D1, C8D1, C10D1, and EOT or PD visit. 
11 Adverse events will be collected for the duration of study therapy and end 30 days after the last dose of study drug. The relationship of the event to itacitinib, 
ECP, GVHD, and other causes (transplant, conditioning regimen, or other immunosuppressants) will be assessed as definite, probable, possible, unlikely, or not 
related. 
12 Hematology includes CBC with differential and platelets. 
13 Chemistry includes a LDH, magnesium, phosphorus, and a CMP (Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, 
Total Bilirubin, Calcium, Carbon Dioxide, Creatinine, Chloride, Glucose, Total Potassium, Protein, Sodium, and Urea Nitrogen). 
14 Coagulation labs include PT/INR and PTT, to be collected at screening and as clinically indicated while on study. 
15 Lipid panel should include total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and VLDL cholesterol. This will occur at C4D1, C7D1, C10D1, 
and EOT or PD visit. 
16 Women of child-bearing potential will require a negative pregnancy test within ≤ 7 days of initiating itacitinib therapy. 
17 HIV and hepatitis testing should include HIV, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, HCV antibody, HBV-DNA, 
and HBC-RNA. HBV-DNA and HBC-RNA are only required if antigen and antibody testing is positive. Prior HIV screening results obtained as standard of care 
for allo-HCT confirming an HIV-negative status may be used for determining eligibility, and tests do not need to be repeated. Prior test results obtained as part of 
standard of care before allo-HCT confirming that a participant is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, surface 
antibody positive) may be used for purposes of eligibility, and tests do not need to be repeated. 
18 Quantitative immunoglobulins to include IgA, IgG, and IgM will be drawn C1D1, C4D1, C7D1, C10D1, EOT or PD visit.  
19 Absolute CD4 Count will be drawn C1D1, C4D1, C7D1, C10D1, EOT or PD visit 
20 Monitoring for infection will be performed at screening and for the duration of study therapy per institutional practice. Testing for cytomegalovirus and 
Epstein-Barr virus will be performed at screening. Prior test results obtained as part of standard of care before allo-HCT may be used for purposes of eligibility 
and tests do not need to be repeated. Routine infection monitoring should occur during the study as per institutional practice and include at a minimum PCR 
 
                                                 

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testing on plasma for CMV and EBV and monitoring for fungal infections (i.e. Aspergillus). Additional monitoring should be performed during treatment if there 
is clinical suspicion of an infection. 
21 Screening assessment may be used if completed within 7 days prior to C1D1. 
22 Graft failure/chimerism should be performed on whole blood and should include: Chimerism, Post-Transplant and Chimerism, Post-Cell Sort, T cells. 
23 Participants will be closely monitored for any evidence of underlying disease relapse or recurrence during study therapy. These evaluations will be conducted 
in accordance with local institutional practices. 
24 To be completed prior to the physical exam at C1D1, C2D1, C3D1, C6D1, C8D1, C10D1, and EOT or PD visit. 
25 ECP will be given at a frequency of twice weekly for 8 weeks followed by a standard taper schedule as per study protocol. Refer to Table 4 for taper schedule. 
26 All patients will undergo 5 to 10 days of itacitinib monotherapy. The first ECP treatment will be considered C1D1. On days that the patient is being seen in 
clinic, itacitinib dosing does not need to be held prior to routine blood draws or for correlative studies. 
27 Patients may be on immune suppression at the time of study enrollment. On days that the patient is being seen in clinic, immunosuppressives should be held 
until after the blood draws if trying to achieve a therapeutic level. See Section 6.1.3. 
28 Correlative studies are only required during dose expansion. On days of drug administration, correlative blood samples should be drawn without regard to 
itacitinib dosing or ECP therapy. Patients should take itacitinib at their usual time.  Blood will be drawn at screening, C1D1, the time of response, C7D1, and at 
EOT or progression, whichever occurs first. 
29 Only to be drawn from the first nine patients enrolled in Part 2, Dose Expansion.  
30 To be collected from participants who complete 12 cycles of therapy. 

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9 
STUDY PROCEDURES 
9.1 
Screening Evaluations 
For screening procedures see the Schedule of Events and the Assessments Section. Screening 
activities may only begin after a subject has signed consent. All screening activities must 
take place within 28 days prior to Cycle 1 Day 1 unless otherwise noted. 
9.2 
Treatment Period 
Once a subject has completed screening, has been found to be eligible, and has been 
registered, treatment procedures may begin. In the absence of disease progression or toxicity, 
patients may continue to undergo 12 cycles of itacitinib therapy. See the Schedule of Events 
and the Assessments Section for treatment period procedures.  
9.3 
Disease progression 
Upon disease progression, study therapy will be discontinued. Procedures required at the 
time of disease progression are noted in the Schedule of Events and should occur at the time 
of identified disease progression. Patients who do not experience disease progression while 
on study therapy will be followed for GVHD progression for 6 months after the end of 
treatment visit. If disease progression occurs during follow-up, the assessments and 
procedures listed on the Schedule of Events will be conducted at the time of progression. 
9.4 
End of Treatment  
End of treatment evaluations will occur 30 days after the last treatment dose of itacitinib. For 
End of Treatment procedures see the Schedule of Events and the Assessments Section. 
9.5 
Follow-up Evaluations 
All patients will be followed for a total of 12 months every 12 weeks (±7 days) after removal 
from study treatment for GVHD progression, initiation of alternative therapy for GVHD, 
relapse of the underlying disease, or death.  Patients removed from the study for unacceptable 
adverse event(s) will be followed until resolution or stabilization of the adverse event. For 
follow-up procedures see the Schedule of Events and the Assessments Section. 
10 Study Assessments 
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the Investigator that may make it unfeasible to perform 
the test. In these cases, the Investigator will take all steps necessary to ensure the safety and well-
being of the patient.  When a protocol-required test cannot be performed, the Investigator will 
document the reason for this and any corrective and preventive actions that he or she has taken to 
ensure that normal processes are adhered to as soon as possible. 

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10.1 Physical Examinations and Vital Signs 
Patients will have physical examinations to include major body systems, vital signs, 
assessment of Karnofsy performance status (see Appendix 1: Karnofsky Performance 
Status), weight and height (height will be measured at screening only) at the time points 
described in the Schedule of Events. If necessary, to facilitate scheduling, the physical exam 
may occur one day prior to study treatment.  
Vital signs, including blood pressure, pulse rate, and temperature will be also recorded at the 
time points described in the Schedule of Events.  Vital signs should be taken prior to the 
administration of any investigational products at the visit. 
Referral to an ophthalmologist or gynecologist/urologist for organ-specific physical 
assessments are allowed per institutional practices. 
10.2 Adverse Events 
Adverse events experienced during trial participation will be collected per the Schedule of 
Events and Adverse Events Section. Each study participant will be questioned about the 
occurrence of adverse events in a non-leading manner. Should the treating investigator feel 
that the adverse event is attributed to study therapy, then dose modification guidelines in the 
Dose Modification Section will be followed.  
10.3 12-Lead Electrocardiograms 
All patients require a single 12-lead ECG measurement according to the Schedule of Events. 
The parameters to be recorded are QT, QTc, PR, and QRS. A standard 12-lead (with a 10-
second rhythm strip) tracing will be used for all ECGs. 
10.4 Laboratory Assessments 
Samples for all laboratory assessments will be drawn at the time points indicated in the 
Schedule of Events and when clinically indicated.  Laboratory tests may be performed up to 
3 days prior to the scheduled clinic visit.  All safety laboratory analyses will be performed by 
the local laboratory for each study center. All safety laboratory assessments must be 
reviewed by the treating investigator prior to study drug administration. When applicable, 
results from the pregnancy test must also be available for review prior to dosing.  
Table 8: Laboratory Assessments 
Laboratory Assessments 
CBC with Platelet Count and Differential 
 
White Blood Cell Count 
 
Hemoglobin 
 
Platelets 
 
Absolute Neutrophil Count 
 
Absolute Lymphocytes 
 Chemistry 
 
Complete Metabolic Panel  
o Sodium 
o Potassium 
o Chloride 
o Carbon Dioxide 

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o Alkaline Phosphatase 
o Aspartate Aminotransferase 
o Alanine Aminotransferase 
o Urea Nitrogen 
o Glucose 
o Creatinine 
o Calcium 
o Protein 
o Albumin 
o Bilirubin 
 
Magnesium 
 
Phosphorus  
 
Lactate Dehydrogenase (LDH) 
Coagulation 
 
PT 
 
INR 
 
PTT 
Quantitative Serum Immunoglobulins 
 
Immunoglobulin A 
 
Immunoglobulin G 
 
Immunoglobulin M 
Lipid Panel 
 
Total cholesterol 
 
Triglycerides  
 
HDL cholesterol  
 
LDL cholesterol 
 
VLDL cholesterol 
HIV and Hepatitis Serologies 
 
HIV 
 
Hepatitis B surface antigen 
 
Hepatitis B surface antibody 
 
Hepatitis B core antibody 
 
HCV antibody 
 
HBV-DNA* 
 
HBC-RNA* 
Infection Monitoring 
 
CMV Quantitative PCR 
 
EBV Quantitative PCR 
Graft Failure/Chimerism 
 
Chimerism, Post-Transplant 
 
Chimerism, Post-Cell Sort, T cells 
Pregnancy 
 
Beta-hCG Qualitative Urine or Serum 
*Only required if antigen and antibody testing is positive.  
10.5 HIV and Hepatitis Serologies 
Participants with active HBV or HCV infection that requires treatment or who are at risk for 
HBV reactivation (i.e. positive HBsAg serology) are excluded from the study. Note: 
Candidates with a positive HBsAg or a negative HBsAg and positive total HBc antibody may 
be included if HBV DNA is undetectable at the time of screening. Candidates positive for 
HCV antibody are eligible only if PCR is negative for HCV RNA. Prior test results obtained 
as part of standard of care before allo-HCT confirming that a participant is immune and not 
at risk for reactivation (i.e., hepatitis B surface antigen negative, surface antibody positive) 
may be used for purposes of eligibility, and tests do not need to be repeated. Participants with 

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positive antigen serology results must have negative PCR results. Participants whose immune 
status is unknown or uncertain must have results confirming immune status before 
enrollment. 
Participants with an active HIV infection are excluded from the study. Prior HIV screening 
results obtained as standard of care for allo-HCT confirming an HIV-negative status may be 
used for determining eligibility, and tests do not need to be repeated. Participants whose HIV 
status is unknown must have results confirming negative status before enrollment. 
10.6 Infection Monitoring 
Monitoring for infection will be performed at screening and for the duration of study therapy 
per institutional practice and will assess for the following at a minimum: Monitoring for 
cytomegalovirus, Epstein-Barr virus, human T-cell lymphotropic virus 1 and 2, and 
Toxoplasmosis IgM and IgG will be performed at screening. Prior test results obtained as 
part of standard of care before allo-HCT may be used for purposes of eligibility and tests do 
not need to be repeated. Routine Infection monitoring should occur during the study as per 
institutional practice and include at a minimum PCR testing on plasma for CMV and EBV 
and monitoring for fungal infections (i.e. Aspergillus).  
Additional monitoring should be performed during treatment if there is clinical suspicion of 
an infection; outcomes should be reported as adverse events as appropriate. 
10.7 Graft Failure and Chimerism Monitoring 
Participants will be monitored for evidence of graft failure during study treatment and post-
treatment follow-up. The monitoring of graft failure will be primarily based on the 
monitoring of blood counts and supported by chimerism studies. Secondary graft failure will 
be defined as a decrease of ANC < 0.5 × 109/L on at least 3 subsequent laboratory 
assessments without another potential etiology or < 95% recipient cells any time after 
engraftment with no signs of relapse. 
Donor chimerism after an allo-HCT involves identifying the genetic profiles of the recipient 
and of the donor pre-transplant and then evaluating the ratio of donor to recipient cells in the 
recipient's blood or bone marrow. Chimerism testing using peripheral blood or bone marrow 
will be performed at the treating investigator's discretion according to local institutional 
practice.  
If a participant experiences graft failure, any action taken to manage the graft including rapid 
taper of immunosuppression, administration of nonscheduled DLI, stem cell boost, or other 
intervention(s) should be documented in the patient’s research chart. 
10.8 Disease Malignancy/Relapse 
Hematologic Disease Relapse Monitoring Participants will be closely monitored for any 
evidence of underlying disease relapse or recurrence at each visit during treatment, EOT, and 
follow-up periods of the study. These evaluations will be conducted in accordance with local 
institutional practices. Details on malignant and nonmalignant hematologic disease relapse 
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10.9 Chronic GVHD Assessment 
GVHD response will be assessed according to the NIH Consensus Development Project 
Criteria. The chronic GVHD activity assessment forms as provided by clinicians and patients 
will also be collected (Appendix 5 and 6). These assessments will occur after two, four, and 
eight weeks of treatment and then monthly thereafter. The primary efficacy endpoint will be 
evaluated at 24 weeks. Patients with responding disease may continue therapy for up to 12 
months.  
10.10 Pulmonary Function Test 
Pulmonary function tests (PFTs) including spirometry with forced expiratory volume in 1 
second (FEV1) and assessment of Diffusing Capacity for Carbon Monoxide (DLCO) is 
required at the Screening Visit. Thereafter, spirometry only is required at protocol-specific 
time-points as defined in the Schedule of Events. PFTs may be conducted ≤ 7 prior to the 
following day one visit to allow for timely review of results. 
10.11 AM-PAC 
The Activity Measure for Post Acute Care (AM-PAC) Basic Mobility Outpatient Routine 
Short Form will be completed at the time-points specified on the Schedule of Events. See 
Appendix 7. 
10.12 2-minute Walk Test 
A 2-minute walk test will be conducted at the time-points specified on the Schedule of 
Events. Patients will be instructed to walk without assistance for 2 minutes and the distance 
traveled in feet will be recorded in the eCRF. Patients should be instructed to walk at the 
fasted speed possible for the entire two minutes, but it is acceptable to slow down or stop as 
necessary. A walk test should not be conducted in the event that a patient is unable to walk 
without assistance and this should be clearly documented in the patient’s chart.  
11 CRITERIA FOR EVALUATION AND ENDPOINT 
11.1 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.  
11.2 Efficacy 
GVHD response will be determined by the NIH Consensus Development Project Criteria 
(see Appendix 4). At each post-baseline assessment, each organ must be assessed using the same 
criteria as for baseline, and response should be determined by comparing the current organ 
assessment with the baseline organ assessment on Day 1. A summary of organ-specific response 
assessment criteria as per NIH consensus guideline is provided below. 

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Table 9: Organ Assessments 
Organ  
Evaluation  
Criteria  
Skin  
NIH Skin Score, considering %BSA  
involvement and sclerotic features  
Change of Skin score  
Eyes  
NIH Eye score  
Change of Eye score  
Mouth  
NIH Modified OMRS (sum of scores for 
erythema, lichenoid, and ulcers)  
Change of OMRS  
Esophagus  
NIH Esophagus score  
Change in Esophagus score  
Upper GI  
NIH Upper GI score  
Change in Upper GI score  
Lower GI  
NIH Lower GI score  
Change of Lower GI score  
Liver  
Lab results for ALT, ALP, and total 
bilirubin  
Change in values of lab results  
Lungs  
NIH Lung score and %FEV1  
Change in %FEV1  
Joints and 
fascia  
NIH Joint and Fascia score and P-ROM 
scores  
Change of Joint and Fascia 
score and P-ROM scores  
 
Table 10: Post-baseline Response Evaluations 
Organ  
Organ-Specific Response  
Skin  
CR/not 
involved  
PR in at least 1 
organ with 
baseline 
involvement 
AND no 
progression in 
any other organ 
(i.e., CR, PR, 
unchanged, or 
no 
involvement)  
PR or CR in 1 
or more organ(s) 
with baseline 
involvement 
AND 
progression in 1 
or more organs 
(incl. new 
occurrence in an 
organ with no 
baseline 
involvement)  
Progression in 
1 or more 
organ(s) with 
baseline 
involvement 
OR new 
occurrence in 
an organ with 
no baseline 
involvement 
AND no CR or 
PR in any other 
organ  
Organ-
specific 
response 
‘unchanged’ 
for all organs 
(incl. no 
involvement)  
Eyes 
Mouth 
Esophagus 
Upper GI 
Lower GI 
Liver 
Lungs 
Joints and 
Fascia 
Overall 
Response 
CR 
PR 
MR 
PD 
Unchanged 
11.3 Stopping Rules 
11.3.1 Part 1 
If two out of six patients have a DLT at the lowest defined dose level (as defined in 
Section 4) attributable to the study therapy, the study will be stopped and re-evaluated.  
11.3.2 Part 2 
A 20% rate of DLT will be considered acceptable and a 30% rate of DLT would be 
unacceptable. Monitoring for excess toxicity will take place quarterly. The trial will be 

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stopped if more than 3/9, 4/13, 5/17, 6/21, 7/26, 8/31, 9/36, 10/40, or 11/45 patients 
treated at the RP2D experience grade 3 or higher non-hematologic adverse events 
attributed to study therapy.  The operating characteristics presented below were 
calculated using the R function “toxbdry” in the package “clinfun”. The output is from 
toxbdry(0.15, 0.4, 7:46, cP0 = 0.1, cP1 = 0.9, ngrid=6). 
Table 11: Probability of stopping 
Operating characteristics of Stopping Rule 
Probability of 
DLT 
Probability of 
Crossing Boundary 
Probability of Stopping 
Before the Last Patient 
Expected Sample 
Size 
0.15 
0.098 
0.098 
43.3 
0.20 
0.304 
0.304 
38.3 
0.25 
0.586 
0.586 
31.1 
0.30 
0.818 
0.818 
23.6 
0.35 
0.942 
0.942 
17.7 
0.40 
0.987 
0.987 
13.7 
12 STATISTICAL CONSIDERATIONS 
12.1 Sample Size Determination 
Part 1  
Part 1 has a maximum of 18 patients. Part 1 has a 3+3 dose de-escalation design with 3 doses 
and a maximum of 6 patients per dose.  
Part 2 
The sample size for Part 2 is 16-46 patients with 6 patients carried over from Part 1 at the RP2D. 
Simon’s optimal two-stage design will be used in Part 2. The primary outcome is the overall response 
rate (CR + PR) at 24 weeks. Withdrawal or progression prior to 24 weeks or missing 24-week 
assessment will be considered non-response. After the first 16 patients treated at the RP2D complete 
24 weeks of therapy or meet treatment discontinuation criteria, enrollment will be put on hold and an 
interim analysis will be conducted. This study treatment will be considered promising if the overall 
response rate at 24 weeks is ≥ 60% and unacceptable if the overall response rate at 24 weeks is ≤40%.   
50% is the reported best overall response rate of current first-line therapy with high-dose steroids. 
The null hypothesis that the true response rate is ≤ 40% will be tested against a one-sided alternative.  
In the first stage of the dose-expansion study, 16 patients will be accrued and followed through the 
first 24 weeks of treatment. Of those 16 patients, 6 patients will be carried over from Part 1 at the 
RP2D. In recognition of a potential accrual pause of at least 24 weeks if all 16 patients are required to 
complete six months of combination therapy, we will permit enrollment of an additional 3 patients 
(20%) after the first 10 eligible patients in the first stage of the dose-expansion study are enrolled if 
no more than 5 of 16 patients have experienced treatment failure (i.e. addition of secondary systemic 
therapy or disease relapse or death) by the end of week 12 of treatment. If there are 7 or fewer 
responses in the first 16 patients enrolled, the study will be stopped. Otherwise, 30 additional patients 

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will be accrued for a total of 46. The null hypothesis will be rejected if 24 or more responses are 
observed in 46 patients. This design yields a type I error rate of 0.0486 and a power of 80% when the 
true response rate is ≥ 60%. 
12.2 Population for analyses 
12.2.1 Part 1 DLT Evaluation 
Subjects must have received ≥ 60% of planned itacitinib doses (21 doses) and ECP 
treatments (4 treatments) during the DLT evaluation period or have had a DLT to be 
evaluable for dose tolerability.  
12.2.2 Evaluable for toxicity 
All patients who have received at least one dose of itacitinib will be evaluable for 
toxicity assessment. 
12.2.3 Evaluable for response 
Patients who have received at least two weeks of combined ECP and itacitinib 
administration will be evaluable for efficacy endpoints. 
12.3 Replacement of Participants 
Part 1 
Any participant who withdraws from the treatment before the completion of the DLT 
evaluation observation period for any reason other than a DLT may be replaced to 
ensure a minimum number of evaluable participants. Participants who do not maintain 
≥ 60% study therapy compliance during the DLT evaluation period and participants 
who have a dose reduction due to concomitant medication use will be replaced. 
Part 2 
Participants will not be replaced unless they fail to begin study treatment.  
12.4 Statistical Analysis 
12.4.1 Primary Endpoint Analysis 
Part 1  
The primary objective is to assess the safety and tolerability of itacitinib and ECP in 
subjects with chronic GVHD and to determine the RP2D. Adverse events (AEs), serious 
adverse events (SAEs), and dose-limiting toxicities (DLTs) are primary endpoints.  
All subjects who receive any study treatment will be included in the final summaries 
and listings of safety data. Detailed information collected for each AE will include a 
description of the event, duration, severity, relatedness to study drugs, action taken, and 
clinical outcome. The severity of the AEs will be graded according to the CTCAE v5.0. 
The statistical analysis of the safety data will be descriptive and tabular in nature.  

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Part 2 
 Simon’s optimal two-stage design will be used in Part 2. The primary outcome is the 
overall response rate (CR + PR) at 24 weeks. Withdrawal or progression prior to 24 
weeks or missing 24-week assessment will be considered non-response. After the first 
16 patients treated at the RP2D complete 24 weeks of therapy or meet treatment 
discontinuation criteria, enrollment will be put on hold and an interim analysis will be 
conducted. This study treatment will be considered promising if the overall response 
rate at 24 weeks is ≥ 60% and unacceptable if the overall response rate at 24 weeks is 
≤40%.   50% is the reported best overall response rate of current first-line therapy with 
high-dose steroids. The null hypothesis that the true response rate is ≤ 40% will be 
tested against a one-sided alternative.  
 In the first stage of the dose-expansion study, 16 patients will be accrued and followed 
through the first 24 weeks of treatment. Of those 16 patients, 6 patients will be carried 
over from Part 1 at the RP2D. In recognition of a potential accrual pause of at least 24 
weeks if all 16 patients are required to complete six months of combination therapy, we 
will permit enrollment of an additional 3 patients (20%) after the first 10 eligible 
patients in the first stage of the dose-expansion study are enrolled if no more than 5 of 
16 patients have experienced treatment failure (i.e. addition of secondary systemic 
therapy or disease relapse or death) by the end of week 12 of treatment. If there are 7 or 
fewer responses in the first 16 patients enrolled, the study will be stopped. Otherwise, 
30 additional patients will be accrued for a total of 46. The null hypothesis will be 
rejected if 24 or more responses are observed in 46 patients. This design yields a type I 
error rate of 0.0486 and a power of 80% when the true response rate is ≥ 60%. 
Exact binomial confidence intervals for response will be reported at the end of the trial.  
12.4.2 Secondary Endpoint Analysis 
Safety 
Toxicity in this trial will be defined as Dose Limiting Toxicities identified in Section 
4.3 attributable to the study therapy. If the observed rate of DLTs exceeds 30% during 
Part 2 portion, the trial will be stopped.  
A safety analysis will be conducted on the safety population, which includes enrolled 
subjects who receive at least one dose of study drug (itacitinib) and one ECP treatment. 
The baseline value is defined as the last value collected on or prior to the first dose date 
of the study drug. The safety variables to be analyzed include exposure of the study 
drug, AEs, clinical laboratory test results, Karnofsky/Lansky performance status, 
physical examination, and vital sign measurements. In general, safety data will be 
tabulated or listed. Descriptive statistics will be used to tabulate toxicities.  

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Efficacy 
 Overall response rate at 1-year as determined by the NIH Consensus 
Development Project Criteria, without secondary systemic immunosuppression 
and no recurrent malignancy or death 
 Failure Free Survival (FFS) at 24 weeks and 1-year as defined as the time from 
the initiation of study therapy until treatment failure defined as the initiation of 
secondary therapy for chronic GVHD, malignancy relapse, or death from any 
cause.  
 The proportion of patients who have withdrawn all immunosuppressants at 1-
year. 
 Overall response rate at 24 weeks, as determined by the NIH Consensus 
Development Project Criteria, stratified by concurrent prednisone (or 
equivalence) use: 0 mg/kg/d, ≤ 0.25mg/kg/d, and > 0.25mg/kg/d. 
 The mean cumulative prednisone dose used at 24 weeks. 
 Organ-specific response rates at 24 weeks and 1-year as determined by the NIH 
Consensus Development Project Criteria. 
 Change in NIH global score of chronic GVHD from baseline to 24 weeks and 1- 
year after the initiation of the protocol therapy. The NIH global score will be 
defined by using the NIH consensus criteria for the assessment of chronic GVHD 
severity. 
 Duration of response (DOR), defined as the interval between the date of initial 
documentation of a response (PR or better), and the time of progression from the 
best response, the start of a new therapy for cGVHD (including corticosteroids), 
or death from any cause. 
 Provider-reported chronic GVHD severity at baseline, 24 weeks, and 1-year.  
 Patient-reported chronic GVHD severity at baseline, 24 weeks, and 1-year. 
 24 week and 1-year non-relapse mortality (NRM) defined as the proportion of 
participants who died due to causes other than a relapse of their primary 
hematologic disease. 
 Relapse rate (RR) of malignant and non-malignant hematologic diseases, defined 
as the proportion of participants whose underlying disease relapses at 24 weeks 
and 1-year.  
 Overall survival (OS) as defined as the time from the initiation of study therapy 
until death from any cause at 24 weeks and 1 year. 
Observed proportions and exact binomial confidence intervals will be reported for binary 
endpoints with no censored events.  These may include withdrawal from 
immunosuppressants at 1-year, the overall response at 24 weeks stratified by current 
prednisone use (0 mg/kg/d, ≤ 0.25mg/kg/d, and > 0.25mg/kg/d.), the overall response at 1 
year, organ-specific response at 24 weeks and 1 year, no recurrent malignancy, no 

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addition of new systemic treatment for chronic GVHD, and use of prednisone dose (or its 
equivalent) of ≤ 0.5 mg/kg/d at 24 weeks. Kaplan-Meier methods will be used for these 
binary endpoints if there are censored events. Kaplan –Meier methods and associated 
confidence intervals will be used for survival endpoints (FFS and OS).  NRM and RR 
will be treated as competing risks and analyzed by computing nonparametric 
subdistribution functions. The minimum, maximum, mean, and median value along with 
interquartile range will be reported for continuous and ordered categorical endpoints 
(NIH global score of chronic GVHD, provider, and patient-reported GVHD severity).  
Change in continuous or ordered categorical endpoints (NIH global score of chronic 
GVHD, provider, and patient-reported GVHD severity) will be analyzed using paired 
Wilcoxon tests.  The minimum, maximum, mean, and median cumulative prednisone 
dose at 24 weeks will be reported, along with the interquartile range.  
12.4.3 Exploratory Endpoint Analysis 
Duration of Response (DOR) 
Duration of response (DOR) is defined as the interval between the date of initial 
documentation of a response (PR or better), and the time of progression from the best 
response, the start of a new therapy for cGVHD (including corticosteroids), or death 
from any cause. DOR will be summarized for all responders. Non-responders will be 
excluded from the analysis of DOR. The median duration of response will be estimated 
using Kaplan-Meier methodology. 
Patient-Reported Outcomes 
As assessed by the change in QOL-SF-36-v2 questionnaire, Lee Chronic GVHD 
Symptom Scale, and Activity Measure for Post Acute Care (AM-PAC) Basic Mobility 
Outpatient Routine Short Form scores at 24 weeks. 
Pharmacodynamics 
The extent of inhibition of JAK1 and STAT phosphorylation in response to relevant 
cytokines, when administered in combination with ECP in subjects with chronic 
GVHD. 
Biomarkers 
To assess the changes in T-cell subsets, B cell population, cytokine expression, and 
other biomarkers of chronic GVHD. 
Socioeconomic Factors 
To evaluate any changes in socioeconomic status (i.e., changes in residence, annual 
income, insurance type, employment status) with cGVHD outcomes and protocol non-
compliance. 
 

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13 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.  
Patients must be registered before receiving any study treatment and must begin treatment 
within five working days after registration.  
To register eligible patients on study, complete a Clinical Trials Office Patient Registration Form and 
submit to CTORegistrations@hci.utah.edu. To register a patient at a site outside of HCI, complete a 
Clinical Trials Office Patient Registration Form, and submit to MultisiteRegistrations@hci.utah.edu. 
14 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. CRF’s 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 a 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. 
15 SPECIAL INSTRUCTIONS  
15.1 
Correlative Studies 
All exploratory/ancillary correlative studies will be performed during the dose-expansion 
study. Exploratory objectives of this study will be to evaluate the effects of JAK1 inhibition 
with ECP on immune effectors post-treatment, evaluate pharmacokinetics and 
pharmacodynamic properties of INCB039110 with ECP, and to measure changes in 
biomarkers of GVHD.  
15.1.1 Blood Correlatives 
Up to 80 mL of blood will be collected at the time points indicated on the Schedule of 
Events. These samples will be used to identify predictive biomarkers, pharmacokinetics, 
pharmacodynamics, and possible mechanisms of resistance.  
Testing may include but is not limited to: 
 Immunohistochemistry. 
 Flow cytometry. 

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 Enumeration and characterization of immune cell populations. 
 Cytokine/chemokines/ interferon assays. 
 DNA/RNA sequencing and analyses. 
 Proteomic analyses.  
 Pharmacokinetics. 
Specimen collection and processing instructions can be found in the lab manual. 
16 ETHICAL AND REGULATORY CONSIDERATIONS 
16.1 Human Subject Protections 
The study will be conducted in accordance with the appropriate FDA, IRB, ICH GCP, and 
other federal and local regulatory requirements, as applicable. Informed consent will be 
obtained from all research participants prior to performing any study procedures using the 
most recent IRB-approved version. All patients must be at least 18 years of age to 
participate. 
16.2 Institutional Review 
Before study initiation, the investigator must have written and dated approval/favorable 
opinion from the IRB/IEC for the protocol, consent form, subject recruitment materials (e.g., 
advertisements), and any other applicable patient-facing documents. The investigator should 
also provide the IRB/IEC with a copy of the Investigator Brochure or product labeling 
information. 
The investigator or designee should provide the IRB/IEC with reports, updates and other 
information (e.g., expedited safety reports, amendments, and administrative letters) according 
to regulatory requirements or institution procedures.  
16.3 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 study classified as high risk per the NCI-approved DSM plan.  
Each high-risk study will be assigned a physician member of the DSMC as a 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 of the medical monitor is required 

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for all dose de-escalations and cohort expansions. All serious adverse events (SAEs) occurring 
in patients treated at HCI or its affiliates will also be reviewed by the full DSMC monthly.  
Each high-risk study will also be assigned a dedicated research compliance officer who will 
monitor the trial. High-risk studies will be monitored by RCO personnel after the first patient 
is enrolled and every three months thereafter during active enrollment. The RCO monitor will 
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.  
16.4 Adverse Events 
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 with the initiation of study therapy and end 30 days 
after the last dose of study drug (or until new cancer treatment is initiated).  
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, recorded and followed as appropriate. 
 The adverse event should be evaluated to determine: 
1. The severity grade based on CTCAE v5.0 (grade 1-5 
2. Its relationship to itacitinib, ECP, GVHD, and transplant associated therapies (i.e. 
transplant, conditioning regimen, or immunosuppressants) (definite, probable, 
possible, unlikely, not related) 
3. Its duration (start and end dates or if continuing at the 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 
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 

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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 itacitinib are described in the 
Drug Information (Section 3) and in the investigator brochure. 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.  
16.4.1 Abnormal Test Findings 
Abnormal test finding, such as incidental image findings, should only be listed as an 
adverse event if it meets the following criteria: 
 Is associated with accompanying symptoms; and/or 
 Requires additional testing or intervention; and/or 
 Leads to changes in study therapy dosing; and/or 
 Leads to the addition or change of a concomitant medication or therapy; and/or 
 It is considered an adverse event by the treating investigator. 
An abnormal test considered to be an error should not be listed as an adverse event. 
Repeating a test due to an abnormal result in the absence of any of the criteria above 
does not require listing as an adverse event.  
16.5 Serious Adverse Event (SAE) 
Information about all serious adverse events will be collected and recorded. A serious adverse 
event is an undesirable sign, symptom or medical condition which: 
 Is fatal or life-threatening 
 Results in persistent or significant disability/incapacity 
 Is medically significant, i.e., defined as an event that jeopardizes the patient or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
 Causes congenital anomaly or birth defect 
 Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
o Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (procedures such as central line placements, paracentesis, 
pain control) 
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since the start of study drug 
o Treatment on an emergency outpatient basis for an event not fulfilling any of the 
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o Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
Collection of serious adverse events will begin the initiation of study treatment and end 30 
days after the last dose of study treatment or until new cancer treatment is initiated, whichever 
happens the soonest. 
Toxicities that fall within the definitions listed above must be reported as an SAE regardless if 
they are felt to be treatment-related or not. Toxicities unrelated to treatment that does NOT fall 
within the definitions above must simply be documented as AEs in the patient research chart.  
16.5.1 SAE Reporting Requirements 
SAEs must be reported to the DSMC, the FDA, the IRB, and Incyte, according to the 
requirements described below: 
A MedWatch 3500A form must be completed and submitted to compliance@hci.utah.edu 
as soon as possible, but no later than 1 working day of first knowledge or notification of 
the event. 
DSMC Notifications: 
 An HCI Research Compliance Officer (RCO) will process and submit the MedWatch 
form to the proper DSMC member as necessary for each individual study.  
 The RCO will summarize and present all reported SAEs according to the Data and 
Safety Monitoring Plan at the monthly DSMC meeting. 
FDA Notifications: 
 Adverse events occurring during the course of a clinical study that meet the following 
criteria will be promptly reported to the FDA: 
 Serious 
 Unexpected 
 Definitely, Probably or Possibly Related to the investigational drug 
 Fatal or life-threatening events that meet the criteria above will be reported within 7 
calendar days after first knowledge of the event by the investigator; followed by as 
complete a report as possible within 8 additional calendar days. 
 All other events that meet the criteria above will be reported within 15 calendar days 
after the first knowledge of the event by the investigator. 
 The RCO will review the MedWatch report for completeness, accuracy, and 
applicability to the regulatory reporting requirements. 
 The RCO will ensure the complete, accurate and timely reporting of the event to the 
FDA. 
 The Regulatory Coordinator will submit the report as an amendment to the IND 
application. 
 All other adverse events and safety information not requiring expedited reporting that 

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occur or are collected during the course of the study will be summarized and reported 
to the FDA through the IND Annual Report. 
IRB Notification: 
 Events meeting the University of Utah IRB or local IRB reporting requirements will 
be submitted per local guidelines. 
Drug Manufacturer Notifications: 
Initial Serious Adverse events (SAEs) and/or subsequent follow-up reports should be 
reported via email to with a cover sheet:  
SafetyReporting@Incyte.com  
Fax (+) 1-866-981-2057.   
16.6 Deaths 
All deaths that occur during the study treatment period, or within the protocol-defined 
follow-up period after the administration of the last dose of study drug, must be reported as 
follows: 
 Death clearly resulting from the disease should be documented in the patient’s 
research chart and eCRF. However, it should not be reported as an SAE. 
 Where death is not due (or not clearly due) to the progression of the disease under 
study, the AE causing the death must be reported as an SAE within 24 hours. 
 Deaths with an unknown cause should always be reported as an SAE.  
 A post-mortem may be helpful in the assessment of the cause of death, and if 
performed, a copy of the post-mortem results should be included in the patient’s 
research chart. 
Deaths occurring after the protocol defined safety follow up period after the administration of 
the last dose of study drug should be documented in the eCRF. If the death occurred as a 
result of an event that started after the defined safety follow up period and the event is 
considered to be due to late onset toxicity to study drug, then it should also be reported as an 
SAE. 
16.7 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 with 30 days of completing the trial or starting another 
new anticancer therapy, whichever is earlier, must be reported to the DSMC, IRB, FDA, and 
the sponsor 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.  

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An “Initial Pregnancy Report” or equivalent must be completed in full and emailed to 
SafetyReporting@Incyte.com. fax (+) 1-866-981-2057 within 24 hours of the discovery of a 
pregnancy of a subject who has taken the Incyte product or the pregnancy of a partner for a 
subject who has taken the Incyte product.  The “Follow-up Pregnancy Report Form” or 
equivalent must be completed and emailed to SafetyReporting@Incyte.com, fax (+) 1-866-
981-2057 within 30 days after delivery so that Incyte is provided with information regarding 
the outcome of the pregnancy. If the pregnancy results in any events which meet the serious 
criteria (i.e., miscarriage or termination), the SAE reporting process needs to be followed and 
the timelines associated with an SAE should be followed. 
16.8 Protocol Amendments 
Any amendments or administrative changes to an IRB approved protocol 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, the scope 
of the investigation, or the scientific quality of the study are required to submit the 
amendment for FDA review. 
16.9 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.  
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 sponsor requires the prompt reporting to HCI RCO of protocol deviations which are: 
 
Exceptions to eligibility criteria. 
 
Intended to eliminate an 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  
16.10 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).  
16.11 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. 

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16.12 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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17 BIBLIOGRAPHY 
1. 
Pasquini MC, and X Z. Current uses and outcomes of hematopoietic stem cell 
transplantation: CIBMTR Summary Slides, 2015 (http://www.cibmtr.org). 
2. 
Lee SJ, Vogelsang G, and Flowers ME. Chronic graft-versus-host disease. Biol Blood 
Marrow Transplant. 2003;9(4):215-233. 
3. 
Flowers ME, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for 
acute graft-versus-host disease and for chronic graft-versus-host disease according to National 
Institutes of Health consensus criteria. Blood. 2011;117(11):3214-3219. 
4. 
Lee JW, and Deeg HJ. Prevention of chronic GVHD. Best Pract Res Clin Haematol. 
2008;21(2):259-270. 
5. 
Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus 
development project on criteria for clinical trials in chronic graft-versus-host disease: I. 
Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-
956. 
6. 
Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus 
Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 
2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 
2015;21(3):389-401 e381. 
7. 
Shulman HM, Kleiner D, Lee SJ, et al. Histopathologic diagnosis of chronic graft-versus-
host disease: National Institutes of Health Consensus Development Project on Criteria for 
Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report. Biol 
Blood Marrow Transplant. 2006;12(1):31-47. 
8. 
Choi J, Cooper ML, Alahmari B, et al. Pharmacologic blockade of JAK1/JAK2 reduces 
GvHD and preserves the graft-versus-leukemia effect. PLoS One. 2014;9(10):e109799. 
9. 
Spoerl S, Mathew NR, Bscheider M, et al. Activity of therapeutic JAK 1/2 blockade in 
graft-versus-host disease. Blood. 2014;123(24):3832-3842. 
10. 
Murphy WJ. Bringing out the DCs' softer side in GVHD. Blood. 2014;124(12):1852-
1853. 
11. 
Flynn R, Du J, Veenstra RG, et al. Increased T follicular helper cells and germinal center 
B cells are required for cGVHD and bronchiolitis obliterans. Blood. 2014;123(25):3988-3998. 
12. 
Carniti C, Gimondi S, Vendramin A, et al. Pharmacologic Inhibition of JAK1/JAK2 
Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects. Clin 
Cancer Res. 2015;21(16):3740-3749. 
13. 
Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-
versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 
2015;29(10):2062-2068. 
14. 
Zeiser R, Burchert A, Lengerke C, et al. Long-Term Follow-up of Patients with 
Corticosteroid-Refractory Graft-Versus-Host Disease Treated with Ruxolitinib [abstract].  
American Society of Hematology: Blood. p. 4561. 
15. 
Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for Glucocorticoid-Refractory Acute 
Graft-versus-Host Disease. N Engl J Med. 2020;382(19):1800-1810. 
16. 
Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for Glucocorticoid-Refractory Chronic 
Graft-versus-Host Disease. N Engl J Med. 2021;385(3):228-238. 
17. 
Knobler R, Barr ML, Couriel DR, et al. Extracorporeal photopheresis: past, present, and 
future. J Am Acad Dermatol. 2009;61(4):652-665. 
18. 
Radojcic V, Pletneva MA, and Couriel DR. The role of extracorporeal photopheresis in 

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chronic graft-versus-host disease. Transfus Apher Sci. 2015;52(2):157-161. 
19. 
Abu-Dalle I, Reljic T, Nishihori T, et al. Extracorporeal photopheresis in steroid-
refractory acute or chronic graft-versus-host disease: results of a systematic review of 
prospective studies. Biol Blood Marrow Transplant. 2014;20(11):1677-1686. 
20. 
Malik MI, Litzow M, Hogan W, et al. Extracorporeal photopheresis for chronic graft-
versus-host disease: a systematic review and meta-analysis. Blood Res. 2014;49(2):100-106. 
21. 
Couriel DR, Hosing C, Saliba R, et al. Extracorporeal photochemotherapy for the 
treatment of steroid-resistant chronic GVHD. Blood. 2006;107(8):3074-3080. 
22. 
Dignan FL, Greenblatt D, Cox M, et al. Efficacy of bimonthly extracorporeal 
photopheresis in refractory chronic mucocutaneous GVHD. Bone Marrow Transplant. 
2012;47(6):824-830. 
 
 
 
 
 

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Appendix 1: Karnofsky Performance Status 
 
Score 
Definition 
100 
Normal, no complaints; no evidence of disease 
90 
Able to carry on normal activity; minor signs or symptoms of disease 
80 
Normal activity with effort, some signs or symptoms of disease 
70 
Cares for self but unable to carry on normal activity or to do active work  
60 
Requires occasional assistance but is able to care for most of personal needs  
50 
Requires considerable assistance and frequent medical care 
40 
Disabled; requires special care and assistance 
30 
Severely disabled; hospitalization is indicated although death not imminent 
20 
Very ill; hospitalization and active supportive care necessary 
10 
Moribund 
0 
Dead 
 
 
Karnofsky DA Burchenal JH. (1949). 'The Clinical Evaluation of Chemotherapeutic Agents in Cancer.' 
In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196. 
 
 
 

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Appendix 2: NIH Criteria Staging of Chronic GVHD 
The definitions for mild, moderate, and severe chronic GVHD are as follows:  
NIH Global Severity of Chronic GVHD  
Mild Chronic GVHD  
 1 or 2 organs involved with no more than score 1 plus  
 Lung score 0  
 
Moderate Chronic GVHD  
 3 or more organs involved with no more than score 1  
OR 
 At least 1 organ or site with a max score of 2  
OR  
 Lung score 1  
 
Severe Chronic GVHD  
 At least 1 organ with a score of 3 
OR  
 Lung score of 2 or 3  
 
Key points:  
 In skin: higher of the 2 scores to be used for calculating global severity.  
 In lung: FEV11 is used instead of clinical score for calculating global severity.  
 If the entire abnormality in an organ is noted to be unequivocally explained by a non-
GVHD documented cause, that organ is not included for calculation of the global 
severity.  
 If the abnormality in an organ is attributed to multifactorial causes (GVHD plus other 
causes), the scored organ will be used for calculation of the global severity regardless 
of the contributing causes (no downgrading of organ severity score).  
 
1 The FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of 
total lung capacity.  
Staging of chronic GVHD as described by Jagasia et al (2015) should be performed using 
scoring criteria as described below.  
 

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Appendix 3: Staging of Chronic GVHD 
Patient Initials: ____________________ 
 
 
 
Patient Number: ___________________  
 
 
Date: _____________________ 
 
 
SCORE 0 
SCORE 1 
SCORE 2 
SCORE 3 
PERFORMANCE 
SCORE:  
 
KPS   ECOG   LPS 
□  Asymptomatic and 
fully active (ECOG 
0; KPS or LPS 
100%) 
□  Symptomatic, fully 
ambulatory, 
restricted only in 
physically 
strenuous activity 
(ECOG 1, KPS or 
LPS 80-90%) 
□  Symptomatic, 
ambulatory, capable 
of self-care, >50%  
     of waking hours out 
    of bed (ECOG 2,  
    KPS or LPS 60-70%)
□  Symptomatic, 
limited self-care, 
>50% of waking 
hours in bed 
(ECOG 3-4, KPS 
or LPS <60%) 
SKIN† 
SCORE % BSA  
 
□  No BSA   involved 
□  1-18% BSA 
□  19-50% BSA 
□  >50% BSA 
 
GVHD features to be scored      
by BSA: 
Check all that apply: 
□ Maculopapular rash/erythema 
□ Lichen planus-like features  
□ Sclerotic features 
□ Papulosquamous lesions or ichthyosis 
□ Keratosis pilaris-like GVHD 
 
 
SKIN FEATURES  
SCORE: 
 
 
□ No sclerotic 
features 
 
 
 
 
□ Superficial  
   sclerotic features “not 
hidebound” (able to 
pinch) 
Check all that apply: 
□ Deep sclerotic             
features  
□ “Hidebound”              
(unable to pinch)  
□ Impaired mobility  
□ Ulceration 
 
Other skin GVHD features (NOT scored by BSA) 
Check all that apply: 
□ Hyperpigmentation 
□ Hypopigmentation 
□ Poikiloderma 
□ Severe or generalized pruritus 
□ Hair involvement 
□ Nail involvement 
 
 
□ Abnormality present but explained entirely by non-GVHD documented cause (specify):_____________________________ 
MOUTH 
□  No symptoms  
□  Mild symptoms 
with disease signs but 
□  Moderate 
symptoms with 
disease signs with 
□  Severe symptoms 
with disease signs on 
examination with 

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Lichen planus-like 
features present: 
□ Yes 
□ No 
not limiting oral 
intake significantly 
partial limitation of 
oral intake 
major limitation of 
oral intake 
□ Abnormality present but explained entirely by non-GVHD documented cause (specify):_____________________________ 
 
SCORE 0 
SCORE 1 
SCORE 2 
SCORE 3 
EYES 
 
Keratoconjunctivitis 
sicca (KCS) confirmed 
by ophthalmologist: 
   □  Yes 
   □  No 
□  Not examined 
 
□  No symptoms  
       
□  Mild dry eye 
symptoms not 
affecting ADL 
(requirement of 
lubricant eye drops  
< 3 x per day)  
 
□  Moderate dry eye 
symptoms partially 
affecting ADL 
(requiring lubricant 
eye drops > 3 x per 
day or punctal 
plugs), WITHOUT 
new vision 
impairment due to 
KCS 
□  Severe dry eye 
symptoms 
significantly 
affecting ADL 
(special eyeware to 
relieve pain) OR 
unable to work 
because of ocular 
symptoms OR loss 
of vision due to 
KCS 
□ Abnormality present but explained entirely by non-GVHD documented cause (specify): ___________________________ 
GI Tract 
 
Check all that apply: 
□  Esophageal web/ 
proximal stricture 
or ring 
□  Dysphagia 
□ Anorexia 
□ Nausea 
□ Vomiting 
□ Diarrhea 
□ Weight loss >5%* 
□Failure to thrive
□   No symptoms 
□ Symptoms without 
significant weight 
loss* (<5%)  
□  Symptoms 
associated with 
mild to moderate 
weight loss*  
(5-15%) OR 
moderate diarrhea 
without significant 
interference with 
daily living  
□ Symptoms 
associated with 
significant weight 
loss* >15%, 
requires nutritional 
supplement for 
most calorie needs 
OR esophageal 
dilation OR severe 
diarrhea with 
significant 
interference with 
daily living  
□ Abnormality present but explained entirely by non-GVHD documented cause (specify):_____________________________ 
LIVER 
 
 
□  Normal total 
bilirubin and 
ALT or AP        
< 3 x ULN 
□ Normal total  bilirubin 
with ALT >3 to 5 x 
ULN or  AP > 3 x 
ULN 
□  Elevated total 
bilirubin but          
<3 mg/dL or      
ALT > 5 ULN 
□  Elevated total         
bilirubin > 3 mg/dL 
□ Abnormality present but explained entirely by non-GVHD documented cause (specify):_____________________________ 
LUNGS** 
 
Symptom score: 
 
 
 
□ No symptoms 
 
 
 
□  Mild symptoms 
(shortness of breath 
after climbing one 
flight of steps) 
 
□  Moderate symptoms 
(shortness of breath 
after walking on flat 
ground) 
 
□  Severe symptoms 
(shortness of breath  
at rest; requiring 02) 
Lung score: 
  % FEV1 
□  FEV1≥80% 
□ FEV1 60-79% 
□  FEV1 40-59% 
□  FEV1 <39% 
Pulmonary function tests  
□   Not performed  

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□ Abnormality present but explained entirely by non-GVHD documented cause (specify):_____________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SCORE 0 
SCORE 1 
SCORE 2 
SCORE 3 
 
 
 
 
 
Joints and Fascia 
 
P-ROM score 
(see below) 
Shoulder (1-7):___ 
Elbow (1-7): ____ 
Wrist/finger (1-7):___ 
Ankle (1-4):___ 
□  No symptoms 
□  Mild tightness of 
arms or legs, normal 
or mild decreased 
range of motion 
(ROM) AND not 
affecting ADL 
□  Tightness of arms 
or legs OR joint 
contractures, 
erythema thought due 
to fasciitis, moderate 
decrease ROM AND 
mild to moderate 
limitation of ADL 
□  Contractures 
WITH significant 
decrease of ROM 
AND significant 
limitation of ADL 
(unable to tie shoes, 
button shirts, dress 
self etc.)  
□ Abnormality present but explained entirely by non-GVHD documented cause (specify):___________________________ 
 
 
 
 
 
GENITAL TRACT  
(See Supplemental figure‡)  
    □  Not examined 
 
Currently sexually active  
□  Yes 
□  No  
  □  No signs  
□ Mild signs‡ and 
females with or 
without discomfort  
on exam  
□  Moderate signs‡ and 
may have  symptoms 
with discomfort on 
exam 
□  Severe signs‡ with   
     or without  
      symptoms   
□ Abnormality present but explained entirely by non-GVHD documented cause (specify):___________________________ 
 
 
 
 
 
Other indicators, clinical features or complications related to chronic GVHD (check all that apply and assign a score 
to severity (0-3) based on functional impact where applicable none – 0,mild -1, moderate -2, severe – 3) 
□ Ascites (serositis)___ 
□  Myasthenia Gravis___ 
 
□ Pericardial Effusion___ 
□  Peripheral Neuropathy___ 
□   Eosinophilia > 500/μl___ 
□ Pleural Effusion(s)___ 
□  Polymyositis___ 
□   Platelets <100,000/μl ___ 
   □ Nephrotic syndrome___ 
□  Weight loss>5%* without GI symptoms ___ □   Others (specify):_____________ 
 
 
 
 
 
 
Overall GVHD Severity  
(Opinion of the evaluator) 
 
 No GVHD 
 
 Mild 
 
 Moderate 
 
 Severe 
 
 
 
 
 
 

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Photographic Range of Motion (P-ROM) 
 
 
 
 
† Skin scoring should use both percentage of BSA involved by disease signs and the cutaneous features scales. When a 
discrepancy exists between the percentage of total body surface (BSA) score and the skin feature score, OR if superficial 
sclerotic features are present (Score 2), but there is impaired mobility or ulceration (Score 3), the higher level should be used 
for the final skin scoring. 
* Weight loss within 3 months. 
**Lung scoring should be performed using both the symptoms and FEV1 scores whenever possible. FEV1 should be used in 
the final lung scoring where there is discrepancy between symptoms and FEV1 scores. 
Abbreviations: ECOG (Eastern Cooperative Oncology Group), KPS (Karnofsky Performance Status), LPS 
(Lansky Performance Status); BSA (body surface area); ADL (activities of daily living); LFTs (liver function 
tests); AP (alkaline phosphatase); ALT (alanine aminotransferase); ULN (normal upper limit). 
‡ To be completed by specialist or trained medical providers. 
 
 
 
_________________________________________   
_____________________________ 
Signature 
 
 
 
 
 
 
Date 
 
 

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Page 83 of 103 
Appendix 4: NIH Criteria for Response Assessment of Chronic GVHD   
 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after 
previous involvement 
Decrease in NIH Skin 
Score by 1 or more points 
Increase in NIH Skin 
Score by 1 or more 
points, except 0 to 1 
Eyes 
NIH Eye Score 0 after previous 
involvement 
Decrease in NIH Eye 
Score by 1 or more points 
Increase in NIH Eye 
Score by 1 or more 
points, except 0 to 1 
Mouth  
NIH Modified OMRS 0 after 
previous involvement 
Decrease in NIH Modified 
OMRS of 2 or more points 
Increase in NIH 
Modified OMRS of 2 or 
more points 
Esophagus 
NIH Esophagus Score 0 after 
previous involvement 
Decrease in NIH 
Esophagus Score by 1 or 
more points 
Increase in NIH 
Esophagus Score by 1 or 
more points, except 0 or 
1 
Upper GI 
NIH Upper GI Score 0 after 
previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper 
GI Score by 1 or more 
points, except 0 or 1 
Lower GI 
NIH Lower GI Score 0 after 
previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower 
GI Score by 1 or more 
points, except from 0 to 1 
Liver 
Normal ALT, alkaline 
phosphatase, and Total 
bilirubin after previous 
elevation of 1 or more 
Decrease by 50% 
Increase by 2 x ULN 
Lungs 
 
Normal % FEV1 after 
previous involvement 
 
If PFTs not available, NIH 
Lung Symptom Score 0 
and P-ROM score 25 after 
previous involvement by at 
least 1 measure 
 
Increase by 10% 
predicted absolute 
value of %FEV1 
 
If PFTs not available, 
decrease in NIH Lung 
Symptom Score by 1 
or more points 
 
Decrease by 10% 
predicted absolute 
value of % FEV1 
 
If PFTs not 
available, increase in 
NIH Lung Symptom 
Score by 1 or more 
points, except 0 to 1 
Joints and 
facia 
Both NIG Joint and Fascia 
Score 0 and P-ROM Score 25 
after previous involvement by 
at least 1 measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more 
points or increase in P-
ROM score by 1 point of 
any site 
Increase in NIH Joint and 
Fascia Score by 1 or 
more points by 1 point 
for any site 
Global 
Clinician overcall severity sore 
0 
Clinician overall severity 
score decreases by 1 or 
more points on a 0-10 
scale 
Clinician overall severity 
score increases by 2 or 
more points on a 0-10 
scale 

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Appendix 5: Clinician Chronic GVHD Activity Assessment   
 

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_________________________________________   
_____________________________ 
Signature 
 
 
 
 
 
 
Date 
 
 

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Appendix 6: Patient Chronic GVHD Activity Assessment   
 
 
 
_________________________________________   
_____________________________ 
Signature 
 
 
 
 
 
 
Date 
 
 

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Appendix 7: AM-PACBasic Mobility Outpatient Routine Short Form 
Patient Initials: ____________________ 
 
 
 
 
Patient Number: ___________________  
 
 
Date: _____________________ 
Please circle the number that reflects your best answer to each question. How much difficulty do you 
currently have…  
(If you have not done an activity recently, how much difficulty do you think you would have if you tried?) 
  
Unable 
A 
Lot 
A 
Little 
None 
 
1. Bending over from a standing position to pick up a piece of clothing 
from the floor, without holding onto anything?  
 
1 
2 
3 
4 
 
2. Standing up from a low, soft couch?  
 
1 
2 
3 
4 
 
3. Taking a 1-mile brisk walk, without stopping to rest?  
 
1 
2 
3 
4 
 
4. Running for 5 minutes on even surfaces?  
 
1 
2 
3 
4 
 
5. Walking several blocks?  
 
1 
2 
3 
4 
 
6. Walking up and down steep unpaved inclines (e.g., steep gravel 
driveway)?  
 
1 
2 
3 
4 
 
7. Running a short distance, such as to catch a bus?  
 
1 
2 
3 
4 
 
8. Carrying something in both arms while climbing a flight of stairs 
(e.g., laundry)?  
 
1 
2 
3 
4 
 
9. Going up and down a flight of stairs outside, without using a 
handrail?  
 
1 
2 
3 
4 
 
10. Making sharp turns when running fast?  
 
1 
2 
3 
4 
 
11. Taking part in strenuous activities (e.g., running 3 miles, 
swimming half mile, etc.)?  
 
 
1 
 
 
2 
 
 
3 
 
 
4 

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12. Standing up from an armless straight chair (e.g., dining room 
chair)?  
1 
2 
3 
4 
 
13. Walking on an uneven surface (e.g., grass, dirt road or sidewalk, 
brick walkways, sidewalks with curb and driveways cuts)?  
 
1 
2 
3 
4 
 
14. Walking around one floor of their home, taking into consideration 
thresholds, doors, furniture, and a variety of floor coverings?  
 
1 
2 
3 
4 
 
15. Doing light housework (e.g., dusting, minor sweeping)?  
 
1 
2 
3 
4 
 
16. Moving up in bed (e.g., reposition self)?  
 
1 
2 
3 
4 
 
17. Getting into and out of a car/taxi (sedan)?  
 
1 
2 
3 
4 
 
18. Cleaning up spills on the floor with a mop?  
 
1 
2 
3 
4 
 
Raw Score: _____________________________ CMS 0-100% Score: _____________________ 
 
Standardized (t-scale) score: _______________ CMS Modifier: __________________________ 
 
 
_____________________________________________ 
_____________________________ 
Signature 
 
 
 
 
 
 
Date 
 

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Appendix 8: Lee Symptom Scale 
Patient Initials: ____________________ 
 
 
 
 
Patient Number: ___________________  
 
 
Date: _____________________ 
By circling one (1) number per line, please indicate how much you have been bothered by the 
following problems in the past month: 
SKIN: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
1. Abnormal skin color  
0 
1 
2 
3 
4 
2. Rashes 
0 
1 
2 
3 
4 
3. Thickened skin 
0 
1 
2 
3 
4 
4. Sores on skin 
0 
1 
2 
3 
4 
5. Itchy skin 
0 
1 
2 
3 
4 
 
 
 
 
 
 
EYES AND MOUTH: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
6. Dry eyes 
0 
1 
2 
3 
4 
7. Need to use eye drops frequently 
0 
1 
2 
3 
4 
8. Difficulty seeing clearly 
0 
1 
2 
3 
4 
9. Need to avoid certain food due to 
mouth pain 
0 
1 
2 
3 
4 
10. Ulcers in mouth 
0 
1 
2 
3 
4 
11. Receiving nutrition from an 
intravenous line or feeding tube 
0 
1 
2 
3 
4 
 
 
 
 
 
 
BREATHING: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
12. Frequent cough 
0 
1 
2 
3 
4 
13. Colored sputum 
0 
1 
2 
3 
4 
14. Shortness of breath with exercise 
0 
1 
2 
3 
4 
15. Shortness of breath at rest 
0 
1 
2 
3 
4 
16. Need to use oxygen 
0 
1 
2 
3 
4 
 
 
 
 
 
 

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EATING AND DIGESTION: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
17. Difficulty swallowing solid foods 
0 
1 
2 
3 
4 
18. Difficulty swallowing liquids 
0 
1 
2 
3 
4 
19. Vomiting 
0 
1 
2 
3 
4 
20. Weight loss 
0 
1 
2 
3 
4 
 
 
 
 
 
 
MUSCLES AND JOINTS: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
21. Joint and muscle aches 
0 
1 
2 
3 
4 
22. Limited joint movement 
0 
1 
2 
3 
4 
23. Muscle cramps 
0 
1 
2 
3 
4 
24. Weak muscles 
0 
1 
2 
3 
4 
 
 
 
 
 
 
ENERGY: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
25. Loss of energy 
0 
1 
2 
3 
4 
26. Need to sleep more/take naps 
0 
1 
2 
3 
4 
27. Fevers  
0 
1 
2 
3 
4 
 
 
 
 
 
 
MENTAL AND EMOTIONAL: 
Not at 
all 
Slightly Moderately Quite a 
bit 
Extremely 
28. Depression 
0 
1 
2 
3 
4 
29. Anxiety 
0 
1 
2 
3 
4 
30. Difficulty sleeping 
0 
1 
2 
3 
4 
 
 
____________________________________ 
 
____________________ 
Signature 
 
 
 
 
 
 
 
Date 
 

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Appendix 9: 36-Item Short Form Survey Instrument (SF-36) 
 
Subject Number: __________________ 
 
 
 
 
Date:_____________ 
 
 

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___________________________________________ 
 
 
__________________ 
Signature 
 
 
 
 
 
 
 
 
Date 
 
 

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Appendix 10: Patient Dosing Diary 
 
Subject Number: _______________________ 
 
 
Date: __________________ 
Itacitinib should be taken once daily (± 8 hours) without regard to food and recorded on the this 
dosing diary. Do not take your dose on days you will be seen by your doctor, but rather hold the dose 
until after your blood is drawn in clinic. If a dose is missed outside of the dosing window, it should 
not be made up, but rather, take the next dose at the regularly scheduled time. 
Date 
Time 
Number of 
tablets taken 
Comments 
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  

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: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
: 
  
 
________________________________________________ 
 
__________________ 
Patient Signature 
 
 
 
 
 
 
 
 Date 
 
 
 

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Appendix 11: AM-PAC Outpatient Conversion Table 
Boston University A M-PA C T M 
Basic Mobility Outpatient Routine Short Form Score Conversion Table 
 
A M-PA C™ 
Raw Score 
A M-PA C™ 
t-Scale 
Score 
Scale Score 
Standard Error 
CMS 0-100% 
score 
CMS 'G Code' 
Modifier 
18 
29.41 
5.21 
100% 
CN 
19 
32.18 
4.57 
94.56% 
CM 
20 
34.18 
4.11 
90.63% 
CM 
21 
36.16 
3.62 
86.74% 
CM 
22 
37.89 
3.24 
83.34% 
CM 
23 
39.36 
2.97 
80.45% 
CM 
24 
40.66 
2.79 
77.89% 
CL 
25 
41.85 
2.68 
75.56% 
CL 
26 
42.95 
2.60 
73.39% 
CL 
27 
44.00 
2.54 
71.33% 
CL 
28 
44.99 
2.49 
69.38% 
CL 
29 
45.94 
2.44 
67.52% 
CL 
30 
46.85 
2.38 
65.73% 
CL 
31 
47.72 
2.32 
64.02% 
CL 
32 
48.57 
2.25 
62.35% 
CL 
33 
49.39 
2.17 
60.74% 
CL 
34 
50.18 
2.10 
59.19% 
CK 
35 
50.95 
2.03 
57.67% 
CK 
36 
51.68 
1.96 
56.24% 
CK 
37 
52.38 
1.91 
54.86% 
CK 
38 
53.05 
1.86 
53.55% 
CK 
39 
53.70 
1.82 
52.27% 
CK 
40 
54.33 
1.79 
51.03% 
CK 
41 
54.95 
1.76 
49.81% 
CK 

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A M-PA C™ 
Raw 
Score 
A M-PA C™ 
t-Scale Score 
Scale Score 
Standard 
Error 
C MS 0-100% 
score 
CMS 'G Code' 
Modifier 
42 
55.57 
1.74 
48.60% 
CK 
43 
56.17 
1.73 
47.42% 
CK 
44 
56.78 
1.72 
46.22% 
CK 
45 
57.38 
1.71 
45.04% 
CK 
46 
57.98 
1.70 
43.86% 
CK 
47 
58.57 
1.69 
42.70% 
CK 
48 
59.16 
1.69 
41.54% 
CK 
49 
59.76 
1.68 
40.36% 
CK 
50 
60.35 
1.68 
39.20% 
CJ 
51 
60.94 
1.68 
38.04% 
CJ 
52 
61.53 
1.69 
36.88% 
CJ 
53 
62.12 
1.69 
35.72% 
CJ 
54 
62.72 
1.71 
34.55% 
CJ 
55 
63.31 
1.72 
33.39% 
CJ 
56 
63.92 
1.74 
32.19% 
CJ 
57 
64.53 
1.77 
30.99% 
CJ 
58 
65.15 
1.80 
29.77% 
CJ 
59 
65.78 
1.84 
28.53% 
CJ 
60 
66.43 
1.88 
27.25% 
CJ 
61 
67.09 
1.93 
25.96% 
CJ 
62 
67.78 
1.99 
24.60% 
CJ 
63 
68.51 
2.06 
23.17% 
CJ 
64 
69.29 
2.15 
21.63% 
CJ 
65 
70.14 
2.27 
19.96% 
CI 
66 
71.07 
2.42 
18.14% 
CI 
67 
72.13 
2.61 
16.05% 
CI 
68 
73.36 
2.87 
13.64% 
CI 
69 
74.72 
3.17 
10.96% 
CI 

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A M-PA C™ 
Raw 
Score 
A M-PA C™ 
t-Scale  Score 
Scale Score 
Standard 
Error 
CMS 0-100% 
score 
CMS 'G Code' 
Modifier 
70 
76.19 
3.49 
8.08% 
CI 
71 
78.20 
3.86 
4.13% 
CI 
72 
80.30 
4.09 
0.00% 
CH 
 
 
AM-PAC TM Basic Mobility Outpatient Routine Short Form Scoring Example 
 
1. Add the number values associated with the response to each item. For example, item 
total yields a Raw Score of 55. 
2. Match the raw score to the t-Scale scores (t-Scale score = 63.31, SE = 1.72). 
3. Find the associated CMS % (CMS % = 33.39%). 
4. Locate the correct CMS Functional Modifier Code, or 'G Code' (G code = C

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