Conditions: Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Myelodysplastic Syndromes Non-Hodgkin Lymphoma Hodgkin Disease
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 55
Healthy volunteers: no

Brief summary:
In this trial, the investigators will begin to explore the possibility that, as in mice, janus kinase inhibitor 1 (JAK1) inhibition with haploidentical-hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) and cytokine release syndrome (CRS) while retaining Graft-versus-Leukemia (GVL) and improving engraftment. The purpose of this pilot study is to determine the safety of itacitinib with haplo-hematopoietic cell transplantation (HCT) measured by the effect on engraftment and grade III-IV GVHD.

Detailed description:

Arms:
arm 1: * Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
* Stem cell transplantation on Day 0
* Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently
* To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure. arm 2: * Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
* Stem cell transplantation on Day 0
* Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently arm 3: -Donors were consented for the patients enrolled in the Safety Lead-In Phase (planned 3 patients). Donors were consented for a second CD34+ collection to use as a rescue in the case of engraftment failure and for collection of a research blood specimen prior to mobilization.

Interventions: intervention 1: Stem cell transplantation intervention 2: Itacitinib intervention 3: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) intervention 4: Human Activity Profile
Intervention descriptions: intervention 1: Standard of care intervention 2: Itacitinib may be taken without regard to food. intervention 3: * Screening, day 14, day 28, day 42, day 74, day 100, taper period, and follow-up (pilot study)
* Screening, day 14, day 28, day 42, day 74, day 100, day 180, taper period, and follow-up period (expansion study) intervention 4: * Screening, day 14, day 28, day 42, day 74, day 100, taper period, and follow-up (pilot study)
* Screening, day 14, day 28, day 42, day 60, day 74, day 100, day 180, taper period, and follow-up period (expansion study)

Protocol document:
Prot_SAP_001.pdf: 
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Page 1 of 81 
Abb1
 
 
A Single-Arm, Open-Label, Pilot Study And Expansion Study of JAK Inhibitor Itacitinib 
for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome after T-
cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation 
 
Washington University School of Medicine 
Division of Oncology 
660 South Euclid Avenue, Campus Box 8056 
St. Louis, MO  63110 
 
Protocol#: 201903114  
IND #: 142205 
ClinicalTrials.gov#:  NCT03755414 
Protocol Version Date: 06/01/2023 
Study Drug: Itacitinib 
 
 
 
 
 
Principal Investigator: 
Ramzi Abboud, M.D. 
Telephone: 314-454-8304 // Fax: 314-454-7551 
Email: rabboud@wustl.edu 
 
Sub-Investigators: 
 
Mark A. Schroeder, M.D. 
Camille Abboud, M.D. 
Amanda Cashen, M.D. 
John F. DiPersio, M.D., Ph.D. 
Todd Fehniger, M.D., Ph.D. 
Francesca Ferraro M.D., Ph.D. 
Armin Ghobadi, M.D. 
Meagan Jacoby, M.D., Ph.D. 
Iskra Pusic, M.D. 
Keith Stockerl-Goldstein, M.D. 
Geoffrey Uy, M.D. 
Ravi Vij, M.D. 
Mathew Walter, M.D.  
Lukas Wartman, M.D. 
John Welch, M.D., Ph.D. 
Peter Westervelt, M.D., Ph.D. 
Tanya Wildes, M.D. 
Terrence Wong, M.D., Ph.D. 
Statistician: 
 
Feng Gao, Ph.D. 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent necessary to obtain 
informed consent, may not be disclosed to another party unless law or regulations require such disclosure.  Persons to 


Version 06/01/23 
 
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whom the information is disclosed must be informed that the information is confidential and may not be further disclosed 
by them 
A Single-Arm, Open-Label, Pilot Study And Expansion Study of JAK Inhibitor Itacitinib 
for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome after T-
cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation 
 
Protocol Revision History 
 
Initial Approval Version 
 
 
 
 
 
 
 
03/01/19 
Amendment #1 
 
 
 
 
 
 
 
 
12/09/19 
Amendment #2 
 
 
 
 
 
 
 
 
07/23/20 
Amendment #3 not approved 
 
 
 
 
 
 
04/28/21 
Amendment #3 
 
 
 
 
 
 
 
 
06/25/21 
Amendment #4 
 
 
 
 
 
 
 
 
02/03/22 
Amendment #5                                                                                                          04/14/22 
Amendment #6 
 
 
 
 
 
 
 
 
07/19/22 
Amendment #7 
 
 
 
 
 
 
 
 
06/01/23 
 
 
 
 


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Pilot Study Schema (Enrolled Prior to Amendment 3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Expansion Phase Schema (Enrolled in Amendment 3 or later) 
 
 
Safety Lead-In Phase (Three Patients): To address concerns of engraftment failure using 
itacitinib throughout the transplant period, for the first three patients we will consent the 
donor for a second CD34+ collection to use as a rescue in the case of engraftment failure.  
If by Day 21 the ANC remains zero, we will start the process to arrange donor cell 
collection.  In the case of engraftment failure at Day 35, itacitinib will be discontinued, the 
donor will undergo apheresis, and product will undergo CD34+ selection per institutional 
standards and infused as soon as possible.  After the first three patients are transplanted 
with an adequate CD34+ dosed product, further enrollment will be held until two of the 
three have achieved engraftment. 
 
 
 


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TABLE OF CONTENTS 
Pilot Study Schema (Enrolled Prior to Amendment 3) ............................................................. 3 
Expansion Phase Schema (Enrolled in Amendment 3 or later) ............................................... 4 
1.0 
BACKGROUND AND RATIONALE ............................................................................ 7 
1.1 
Graft-versus-Host Disease and Cytokine Release Syndrome after Haploidentical 
Peripheral Blood Hematopoietic Cell Transplantation ......................................................... 7 
1.2 
Investigational Agent:  Itacitinib (INCB039110, Incyte Corporation) .................. 15 
1.3 
Study Rationale ........................................................................................................... 17 
2.0 
OBJECTIVES ................................................................................................................. 18 
2.1 
Pilot Study Objectives................................................................................................. 18 
2.2 
Expansion Phase Objectives....................................................................................... 18 
3.0 
PATIENT SELECTION ................................................................................................ 19 
3.1 
Inclusion Criteria ........................................................................................................ 19 
3.2 
Exclusion Criteria ....................................................................................................... 20 
3.3 
Additional Inclusion Criteria Under Amendment 5 ................................................ 21 
3.4 
Eligibility of Women and Minorities ......................................................................... 21 
4.0 
REGISTRATION PROCEDURES ............................................................................... 21 
4.1 
Confirmation of Patient Eligibility ............................................................................ 21 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database ................. 22 
4.3 
Assignment of UPN ..................................................................................................... 22 
5.0 
TREATMENT PLAN ..................................................................................................... 22 
5.1 
Overall Treatment Plan .............................................................................................. 22 
5.2 
Evaluability .................................................................................................................. 22 
5.3 
Replacement of Ineligible Patients ............................................................................ 23 
6.0 
ADMINISTRATION OF PROTOCOL TREATMENT ............................................. 23 
6.1 
Conditioning Regimens for Transplant .................................................................... 23 
6.2 
Standard of Care GVHD Prophylaxis ...................................................................... 24 
6.3 
Stem Cell Transplantation (Day 0) ............................................................................ 24 
6.4 
Itacitinib ....................................................................................................................... 24 
6.5 
General Concomitant Medication and Supportive Care Guidelines ..................... 28 
6.6 
Prohibited Medications .............................................................................................. 28 
6.7 
Women of Childbearing Potential ............................................................................. 29 
6.8 
Treatment of Acute GVHD ........................................................................................ 29 
6.9 
Failure to Engraft ....................................................................................................... 29 
6.10 
Duration of Therapy ................................................................................................... 29 
6.11 
Post-Treatment Follow-Up ......................................................................................... 30 
6.12 
End of Study Definition .............................................................................................. 30 
6.13 
Definition of Completed Patients ............................................................................... 30 
7.0 
PHARMACEUTICAL INFORMATION ..................................................................... 30 
7.1 
Itacitinib ....................................................................................................................... 30 
8.0 
STUDY CALENDAR ..................................................................................................... 33 
8.1 
Pilot Study.................................................................................................................... 33 


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8.2 
Expansion Study.......................................................................................................... 34 
9.0 
SCHEDULE OF ASSESSMENTS ................................................................................ 35 
9.1 
Screening ...................................................................................................................... 35 
9.2 
Treatment Schedule and Assessments ...................................................................... 35 
10.0 
CORRELATIVE STUDIES ........................................................................................... 42 
10.1 
Correlative Studies Background ............................................................................... 42 
10.2 
Questionnaires ............................................................................................................. 43 
11.0 
DATA SUBMISSION SCHEDULE .............................................................................. 44 
11.1 
Pilot Study.................................................................................................................... 45 
11.2 
Expansion Phase.......................................................................................................... 45 
11.3 
Adverse Event Collection in the Case Report Forms .............................................. 46 
12.0 
REGULATORY AND REPORTING REQUIREMENTS ......................................... 46 
12.1 
Sponsor-Investigator Reporting Requirements ....................................................... 46 
12.2 
Exceptions to Expedited Reporting ........................................................................... 49 
13.0 
DATA AND SAFETY MONITORING ........................................................................ 49 
14.0 
STUDY EFFICACY AND DISCONTINUATION ...................................................... 50 
14.1 
Criteria to Measure Incidence and Severity of GVHD ........................................... 50 
14.2 
Definitions for Safety and Efficacy Assessments...................................................... 50 
14.3 
Response Review ......................................................................................................... 52 
15.0 
STATISTICAL CONSIDERATIONS .......................................................................... 52 
15.1 
Study Design ................................................................................................................ 52 
15.2 
Study Endpoints .......................................................................................................... 52 
15.3 
Sample Size Calculation ............................................................................................. 53 
15.4 
Statement of Feasibility .............................................................................................. 54 
15.5 
Statistical Analyses...................................................................................................... 54 
16.0 
REFERENCES ................................................................................................................ 59 
APPENDIX 1: ECOG Performance Status Scale .................................................................... 63 
APPENDIX 2: Acute GVHD Assessment ................................................................................. 64 
APPENDIX 3: Chronic GVHD Assessment ............................................................................. 66 
APPENDIX 4: FACT-BMT (Version 4) ................................................................................... 69 
APPENDIX 5: Human Activity Profile..................................................................................... 72 
APPENDIX 6: Immunosuppressive Medication Questionnaire ............................................ 74 
APPENDIX 7: ASTCT CRS Grading System.......................................................................... 75 
APPENDIX 8: Medication Diary .............................................................................................. 76 
APPENDIX 9: Definitions for Adverse Event Reporting ....................................................... 77 
APPENDIX 10: Reporting Timelines........................................................................................ 79 
 


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1.0 
BACKGROUND AND RATIONALE 
 
1.1 
Graft-versus-Host 
Disease 
and 
Cytokine 
Release 
Syndrome 
after 
Haploidentical Peripheral Blood Hematopoietic Cell Transplantation  
 
1.1.1 Haploidentical Peripheral Blood Hematopoietic Cell Transplantation  
 
Allogeneic hematopoietic cell transplantation (HCT) is a cornerstone of therapy for 
hematologic malignancies, often constituting the only curative intent treatment 
available. HLA-matched sibling donors have historically offered the best clinical 
results, but are unavailable for the majority of patients. HLA-matched unrelated 
donors (MUD) are traditionally considered second line, but availability is limited, 
especially for ethnic minorities1,2. In contrast, the majority of patients have readily 
available related haploidentical donors.  Therefore, haploidentical HCT (haplo-
HCT) offers a crucial alternative to traditional HLA-matched HCT. Several studies 
have shown that haplo-HCT patients have outcomes equivalent to those of HLA-
matched unrelated donor transplantations3,4. Recent advances utilizing post-
transplantation cyclophosphamide (PTCy) have allowed for selective depletion of 
post-transplantation alloreactive T cells while maintaining the graft-versus-
leukemia effect and acceptable rates of graft-versus-host disease (GVHD) among 
recipients of haplo-HCT5–10. Furthermore, haplo-HCT are less costly and faster 
compared with matched unrelated donor transplants.  Both donor bone marrow and 
peripheral blood are viable sources for haplo-HCT grafts. Peripheral blood stem 
cells as a donor option provide larger donor T cell doses, which has been associated 
with lower relapse rates but may bring added toxicities, including higher incidence 
of GVHD and cytokine release syndrome3,5,10–12.  At our institution, rates of GVHD 
and engraftment failure after haplo-HCT were similar between patients who 
underwent myeloablative conditioning and reduced intensity conditioning13.  
Donor source may have a significant effect on rate of primary graft failure.  In a 
large retrospective analysis performed by the Center for International Blood and 
Marrow Transplant Research group, patients receiving haplo-HCT from parent 
donors had a significantly higher rate of graft failure compared with either sibling 
or offspring donor sources (14% vs. 6 and 7% respectively, p=0.02)12. 
 
1.1.2 Graft versus Host Disease 
 
1.1.2.1 Background 
 
Allogeneic bone marrow transplant (BMT) cures leukemia by means of 
cytoreduction induced by the preparative regimen and by transfer of 
immunocompetent alloreactive donor T cells from the bone marrow 
allograft that exert an anti-leukemic effect called the Graft-versus-
Leukemia (GVL) effect14.  The International Bone Marrow Transplant 
Registry (IBMTR) analyzed data from 2,254 patients who underwent HLA-
identical sibling BMT for leukemia (Chronic Myeloid Leukemia [CML] in 
chronic phase, AML and Acute Lymphoblastic Leukemia [ALL] in first 


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remission).  After adjusting for other variables that affect relapse, they 
showed that there was a statistically significant reduction in the relapse 
risk for patients who developed GVHD, especially chronic GVHD14. 
Thus, with traditional transplantation approaches, the GVL and GVHD 
effects are coupled.  
 
Despite the positive impact on reducing disease recurrence after transplant, 
the negative impact of acute GVHD on morbidity and mortality after 
allogeneic transplant is significant. According to a recent study by the 
CIBMTR15 including 4224 patients with AML and 1517 patients with MDS, 
those patients that develop acute GVHD after transplant have an increased 
risk of treatment related mortality (HR 2.51 (95% CI 2.18 – 2.89)), and 
lower overall survival (HR 1.71 (95% CI 1.55 – 1.89)) based on a time 
dependent multivariate analysis. Our own institutional incidence of acute 
GVHD after allo-HSCT is similar to that reported by the CIBMTR registry. 
Clinically significant acute GVHD occurred in 52–66% of recipients of 
unrelated donor transplants and life threatening acute GVHD occurred in 
17–21% of recipients. This is similar to incidence in our haplo-HCT 
patients: clinically significant acute GVHD occurred in 40-50% of 
recipients and life threatening acute GVHD occurred in 10-15% of 
recipients. Acute GVHD remains a significant problem in our patients; thus, 
finding a means to harness the GVL effect while reducing or 
eliminating GVHD is a major goal in designing novel transplant trials.  
 
Both donor bone marrow and peripheral blood are commonly used graft 
sources in haplo-HCT.  Peripheral blood grafts contain much higher T-cell 
doses compared with bone marrow grafts, which affects toxicities and 
patterns of failure.  The Center for International Blood and Marrow 
Transplant Research group published their experience after 681 haplo-
HCTs – 481 bone marrow and 190 peripheral blood, showing similar overall 
survival between donor sources16.  Consistent with other donor types, rates 
of acute GVHD were significantly lower with bone marrow vs. peripheral 
blood grafts (25% vs. 42%, p < 0.001) and for severe grade III-IV acute 
GVHD, trended towards lower rates (7% vs. 10%, p=0.30).  The rates of 
chronic GVHD were also lower with bone marrow grafts (20% vs. 41%, p 
= 0.001).  Conversely, the 2-year rate of relapse/progression was higher 
with bone marrow grafts (45% vs. 28%, p < 0.001).  This finding again 
highlights the role of T-cells in both GVHD and GVL, and the challenge 
inherent in reducing GVHD without compromising GVL.   
 
Both GVL and GVHD are largely driven through T-cell activity, and both 
phenomena can be abrogated through T-cell depleted transplantation17. 
Published data and our preclinical data (see Section 1.1.4) demonstrate that 
the IFNγ and IL-6 cytokine pathways and downstream JAK1 and JAK2 
signaling are central to this process.  Acute GVHD remains a significant 
problem in our study population; thus, finding a means to harness the GVL 


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effect while reducing or eliminating GVHD is a major goal in designing 
novel transplant trials.  We anticipate that modulation of these pathways 
in the peri-transplant period provides an opportunity to decouple GVL 
and GVHD effects (see Sections 1.1.5 and 1.1.6).  
 
Peripheral blood grafts have the additional advantage of ease and lower cost 
of collection of donor stem cells.  JAK1 inhibition may reduce the rate of 
GVHD after peripheral blood haplo-HCT to rates similar to bone marrow 
grafts, which at a minimum would expand access to haplo-HCT.  Ideally, 
we would achieve a reduction in GVHD while retaining lower relapse rates, 
leading to better overall survival in patients undergoing haplo-HCT. 
 
In the trial described here we will begin to examine the safety and 
effectiveness of itacitinib treatment administered with haplo-HCT as 
GVHD prophylaxis.  
 
1.1.2.2 Biomarkers for Acute GVHD 
  
Currently, the gold standard for diagnosis of GVHD is biopsy of affected 
tissue.  A number of efforts have been made to establish biomarkers for the 
diagnosis and prognosis of acute GVHD.  A serum biomarker panel would 
represent a safe and noninvasive tool to establish this vital diagnosis.  
Predictive information could be used to determine which patients need more 
intensive therapy than steroids alone.  One example of these efforts is the 
Ann Arbor GVHD score, which has been used as a predictor of steroid 
responsiveness in acute GVHD.  It involves the measurement of 
concentrations of TNFR1, ST2, and REG3-alpha at the time of GVHD 
diagnosis, and a higher score was associated with steroid refractoriness and 
poor outcome18.  These panels have not been validated in the haplo-HCT 
setting.   
 
1.1.3 Cytokine Release Syndrome 
 
1.1.3.1 Background  
 
The cytokine release syndrome (CRS) has been described as fevers, 
vascular leak, hypotension, and respiratory and renal insufficiency in the 
context of dysregulated immune responses19–21. CRS is characterized by 
high levels of inflammatory cytokines, including IL-6, interferon-γ, IL-2, 
and high peaks of C-reactive protein (CRP) and ferritin that result from 
robust activation of the immune system. This syndrome was described after 
monoclonal antibody therapy and is now recognized as a common toxicity 
after chimeric antigen receptor (CAR) T cell, dual-affinity re-targeting 
antibody (DART), and other immunotherapies19,22–30.  We published the 
first description of CRS after haplo-HCT in 201631, recently confirmed by 
a second report from another institution (Raj, Chhabra et al, BBMT, 


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https://doi.org/10.1016/j.bbmt.2018.04.010).  
 
Neurotoxicity is a common and highly morbid clinical feature of CRS that 
has been described in numerous settings28,29,32,33.   Transient 
cardiomyopathy, likely similar to cardiomyopathy of sepsis or stress-
cardiomyopathy, has also been described in this highly inflammatory 
setting19,34.  This study will use ASTCT criteria to grade CRS (Appendix 7). 
 
 
Given the central role of IL-6 in the pathophysiology of CRS (see references 
and Sections 1.1.4 and 1.1.5), anti–IL-6 and anti–IL-6 receptor therapies 
such as tocilizumab and siltuximab have been used to disrupt the toxic 
effects associated with CRS27,35. Tocilizumab treatment of CRS after CAR 
T cell infusion results in rapid defervescence and stabilization of blood 
pressure within 48 hours24,27,31. We anticipate that JAK inhibition, which 
acts downstream of IL-6, provides an opportunity to reduce CRS 
incidence and severity after haplo-HCT (see Sections 1.1.5 and 1.1.6).  
 
In the trial described here we will begin to examine the safety and 
effectiveness of itacitinib treatment administered with haplo-HCT as CRS 
prophylaxis. 
 
1.1.3.2 Outcomes Worse in Haplo-HCT Patients who Experience Severe 
CRS 
 
 
We previously described the occurrence of severe CRS after haplo-HCT 
and its association with poor clinical outcomes, including increased 
transplant related mortality, inferior overall survival, and delayed 
engraftment31.  Of the 169 patients who have undergone haplo-HCT at our 
institution, 91% have suffered CRS, and 16% have suffered severe CRS. 
Severe CRS was associated with significant reduction in overall survival 
(median 7.5 months vs. not yet reached, p < 0.0001) and increased 
transplant related mortality at 100 days and one year (7.8% vs. 20.8%, 
11.9% vs. 30.7%, p <0.015). Two groups have since published comparable 
rates of CRS after peripheral blood haplo-HCT, as well as poor clinical 
outcomes for patients suffering from severe CRS36,37.  In 38 patients 
undergoing peripheral blood haplo-HCT, Mariotti et al found an 18% 
incidence of severe CRS associated with worse 1y-NRM compared with 
CRS <3: 78% (95% CI: 6-98) vs 20% (95% CI: 8-37) (p=0.002).  Yasser et 
al found a 29% incidence grade 4 CRS, associated with faster NK cell 
recovery but slower CD4 cell recovery.  In our published data, and 
consistent with the above results, the association between CRS and poor 
outcomes persisted beyond the window of CRS, implying there is a long 
term deleterious impact from CRS.  Therefore, a prophylactic approach 
using a JAK inhibitor may be effective in improving long-term 
outcomes for these patients by preventing CRS.   
 


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1.1.3.3 Engraftment Failure is High in Patients with DSAs and Severe CRS 
 
 
In our patients undergoing haplo-HCT, our overall rate of delayed 
neutrophil engraftment at day 28 was 10%13,31, with a higher rate in patients 
with donor specific antiboodies (DSAs).  .  We also found a higher rate of 
delayed engraftment in patients suffering from severe CRS vs. mild and no 
CRS, with a hazard rate of engraftment three times higher in patients with 
mild or no CRS (p = 0.0003, Figures 1 and 2)38.  While there are concerns 
of engraftment delay with a JAK inhibitor, reduction in CRS may in 
fact lead to similar or improved engraftment.  Critically important, we 
have built in a safety lead in phase to this study to provide a rescue product 
for patients in cases of engraftment failure (see Section 5.2).  Furthermore, 
engraftment rate is a primary safety endpoint and we will perform 
continuous monitoring with predefined stopping rules, ensuring that safety 
is assessed after every event (see Section 15). 
 
 
 
Figure 1: Neutrophil Engraftment by CRS Grade 
 
 
Figure 2: Platelet Engraftment by CRS 
Grade 
 
 
1.1.4 GVHD and patients with CRS after haplo-HCT   
 
Peripheral blood haplo-HCT is associated with a lower rate of relapse, but it’s 
complicated by CRS and higher GVHD, with a net neutral effect on survival16,31.  
In our institutional analysis, the incidence of moderate (grades II to IV) and severe 
(grades III to IV) acute GVHD (aGVHD) was not significantly elevated in patients 
with severe CRS compared with the rest of the cohort31.  Similarly, there was no 
difference in chronic GVHD.  However these analyses were limited by the small 
number of patients with severe CRS.   The incidence of grade II to IV aGVHD in 
patients with severe CRS vs. the rest of the cohort was 22% vs. 33% (P = .71).  The 
incidence of grade III to IV GVHD in patients with severe CRS vs. the rest of the 
cohort was 11% versus 13% (P = 0.99).  In patients surviving to Day 80, there was 
no statistically significant difference in chronic GVHD between patients with 


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severe CRS and the rest of the cohort (17% versus 51%, P = .20).  Incidences of 
GVHD and CRS in peripheral blood replete haplo transplants are high, and 
both independently contribute to morbidity and mortality. 
 
 
1.1.5 Preclinical Data  
 
1.1.5.1 IFNγ and IL-6 pathways are upregulated in CRS 
 
 
Multiple groups, including our own, have shown that CRS after haplo-HCT, 
CAR-T cell, dual-affinity re-targeting antibody, and other immunotherapies 
is associated with elevated IFNγ and IL-6 levels19,20,24,27,31,39 
 
1.1.5.2 T-Cell Secreted IFNγ induces Monocytes to secrete IL-6 in in-vitro 
models of CRS  
 
Preclinical data suggests that inhibition of IFNγ and IL-6 pathways reduces 
cytokine release syndrome.  Singh et al showed in an in vitro model of CAR 
T-cell mediated CRS, that IFNγ is secreted by CAR T-cells40.  This induces 
IL-6 secretion by monocyte-lineage cells through a contact-independent 
mechanism.  It may be possible to inhibit these pathways while relatively 
preserving T-cell cytotoxic anti leukemia effects. 
   
 
1.1.5.3 JAK1/2 inhibition prevents IL-6 secretion by monocytes in in vitro 
models of CRS  
 
We have generated an in vitro model of CRS that uses cytotoxic activated 
T-cells, macrophage linage cells, and activating beads.  The combination of 
these reagents led to increased levels of IFNγ and IL-6, similar to CRS.  The 
addition of Ruxolitinib led to a 50% decrease in both IFNγ and IL-6 levels 
(Unpublished).  This supports our hypothesis that Jak1/2 inhibition could 
be used to blunt the pathologic increases in IL-6 levels seen in haplo 
transplant. 
 
 
 
 
Figure 3. Role of IFNγR signaling in alloreactive donor T cells. 
IFNγR-/- T cells do not cause lethal GVHD in a B6 to Balb/c major 
MHC-mismatched allo-HSCT model. 


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1.1.5.4 IFNγ and IL-6 blockade and JAK Inhibition Reduce GVHD and 
Increase Tumor Cell Death in mouse models  
 
 
Acute GVHD is associated with an inflammatory cytokine profile with 
overlapping features to that of CRS.  Common inflammatory cytokines 
increased in acute GVHD are IL1, IL-6 and IFNγ. T-cell activation by 
inflammatory cytokines is mediated mainly through JAK 1, and 2 kinases. 
STAT1 and STAT3 are downstream of JAK1 and 2 and have been shown 
to be critically important to the development of acute GVHD in mouse 
models41,42.  We and others have recently published preclinical data 
Figure 4. Combined IFNγR and IL-6 blockade prevents GVHD. T 
cells do not cause lethal GVHD in a B6 to Balb/c major MHC-
mismatched allo-HSCT model when IFNγ and IL-6 pathways are 
inhibited. 
0
10
20
30
40
50
60
0
20
40
60
80
100
days after allo-HSCT
% survival
TCD BM (n=13)
WT T + iso (n=27)
WT T + anti-IL6R Ab (n=25)
γR-/- T + iso (n=26)
γR-/- T + anti-IL6R Ab (n=25)
*p=0.0156
 
Figure 5. Combined IFNγR and IL-6 blockade associated with 
higher hematopoietic cell counts. 
Figure 6. Jak1/2 inhibition combined with T-cell therapy 
increased tumor cell death above T-cell therapy alone. 


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highlighting the importance of interferon receptor gamma signaling in 
mediating the trafficking of effector T cells in aGVHD43,44.   
 
Recently 
published 
institutional 
research 
demonstrates 
that 
IFNγR/IL6R or downstream JAK1/JAK2 are optimal targets to 
prevent GVHD and to reverse ongoing GVHD while preserving or 
enhancing both GVL effects and multi-lineage hematopoietic 
reconstitution after MHC-mismatched allo-HSCT45.  Mice transplanted 
with MHC-mismatched T cells genetically deficient in interferon gamma 
receptor (IFNγR -/-) have decreased aGVHD and improved survival (Figure 
3).  Furthermore, IL-6 inhibition combined with IFNγR-/- leads to complete 
prevention of aGVHD (Figure 4).  Consistent with this, we saw higher 
hematopoietic cell counts in the combined blockade group (Figure 5). 
  
Finally, the addition of JAK inhibition with mismatched T-cell 
transplantation led to increase tumor cell death compared with 
transplantation without JAK inhibition.  
 
1.1.6 Clinical Data  
 
1.1.6.1 IL-6 Inhibition for the prevention of CRS and GVHD 
 
 
As outlined above, tocilizumab, a monoclonal antibody against IL-6R, has 
become standard of care for the treatment of CRS in multiple settings.  It is 
rapidly effective in abrogating the symptoms of CRS.  This agent is now 
being explored for prevention of both CRS and GVHD.  Kennedy et al 
performed a pilot phase 1/2 study using single dose tocilizumab on Day -1 
before sibling or unrelated fully matched T-cell replete stem cell 
transplantation for GVHD prophylaxis35.  They treated 48 patients with 
tocilizumab and compared them with 54 consecutive control patients, 
finding no difference in TRM, infections, or engraftment.  In the treatment 
group, they found lower than expected rates of acute GVHD (12%).  
Because JAK 1 and 2 inhibitors act downstream of the IL-6R, it is 
biologically plausible that these agents would be as or more effective 
that tocilizumab or siltuximab (a monoclonal antibody against IL-6R) 
at preventing CRS and GVHD. 
 
1.1.6.2 JAK Inhibitors for GVHD prophylaxis 
 
 
Morozova et al used post-transplant cyclophosphamide and ruxolitinib, a 
JAK inhibitor, for GVHD prophylaxis after hematopoietic cell 
transplantation in patients with myelofibrosis46.  Their prospective pilot 
study has enrolled 13 patients to date, with nine 10/10 MUDs, one 9/10 
MUD, and two haploidentical donors.  They used a ruxolitinib dose of 45 
mg/day on Days -7 to -2 and then 15 mg/day on Days 5 to 100.  The regimen 
was safe with acceptable toxicities.  Engraftment was attained in all patients, 
although two required additional stem cell infusion.  Notably, the ruxolitinib 


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dose was reduced to 10 mg/day in all but two patients secondary to poor 
graft function. However, they had encouraging rates of acute GVHD: two 
patients developed grade III aGVHD and one developed grade II aGVHD.  
Four patients developed cGVHD, and all but one were successfully treated 
with cyclosporine A without steroids. 
     
 
1.2 
Investigational Agent:  Itacitinib (INCB039110, Incyte Corporation)  
 
Itacitinib adipate is a novel, potent, and selective inhibitor of the JAK family of protein 
TYKs with selectivity for JAK1.  Itacitinib is an investigational product that is proposed 
for development for treatment of MPNs, including MF; inflammatory diseases, including 
RA and psoriasis; 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. 
 
In this trial we hope to extend to patients the observation from our mouse model that 
itacitinib treatment with haplo-HCT will reduce the incidence of both grade III-IV acute 
GVHD and severe CRS, while preserving or improving GVL effect and engraftment.  
Itacitinib (see Section 7.1) is under active evaluation for treatment of GVHD.  Furthermore, 
itacitinib is currently being evaluated for GVHD prophylaxis in patients undergoing 
matched related or matched unrelated peripheral blood hematopoietic cell transplantation 
(GRAVITAS-119, NCT03320642).  As a JAK1 selective inhibitor, it may be effective at 
preventing both GVHD and CRS without increasing incidence of engraftment failure.  
 
1.2.1 Pharmacology 
 
Itacitinib potently inhibits JAK1 (IC50 = 3.6 nM at 1 mM adenosine triphosphate 
concentration), with 22- to > 500-fold selectivity over the other JAK family 
members, JAK2, JAK3, and TYK2.  It does not significantly inhibit (< 30% 
inhibition) a broad panel of approximately 60 other kinases.  Itacitinib is also potent 
(IC50 values of approximately 10 nM to 350 nM) in cytokine-driven cell-based 
assays.  This effect is not due to general cytotoxicity.  Itacitinib also inhibits the 
growth of the cytokine-dependent cell line INA-6.  Itacitinib potently inhibits the 
phosphorylation of STAT proteins and the production of proinflammatory factors 
induced by other cytokines, such as IL-23 and IL-6 with IC50 values of 
approximately 30 nM to 100 nM.  In contrast, itacitinib shows less inhibition in 
cell-based assays dependent on JAK2 with IC50 values of approximately 1 μM 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 WT JAKs when administered by continuous infusion, achieving 
plasma concentrations well below those necessary to inhibit JAK2.  Oral itacitinib 
also reduced splenomegaly in a model of JAK2 V617F–driven neoplasia relevant 
to MF.   
 


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1.2.2 Clinical Studies 
 
 
As of 12/13/2016, 10 Phase 1, 3 Phase 1/2, and 5 Phase 2 clinical studies with 
itacitinib, including studies of itacitinib in combination with chemotherapeutic 
agents, corticosteroids, pembrolizumab (anti–PD-1 monoclonal antibody), and 
investigational PI3Kδ (INCB040093 and INCB050465) and IDO1 (epacadostat) 
inhibitors, have either been completed or are ongoing.  A total of 777 subjects were 
enrolled in these studies and received at least 1 dose of itacitinib.  In completed 
clinical pharmacology studies, itacitinib has been administered to 197 healthy adult 
subjects as a single dose, repeat single doses, or multiple doses for up to 10 days. 
 
In ongoing and completed clinical pharmacology studies, itacitinib was generally 
safe and well-tolerated in healthy subjects, with few discontinuations.  The majority 
of TEAEs were mild in severity.  There have been no clinically significant, 
unanticipated safety findings or trends observed.  The main drug effect identified 
was a rapidly reversible dose-related decrease in neutrophil counts presumably 
caused by neutrophil margination; neutrophil decreases generally resolved within 
24 to 48 hours of dose discontinuation.  Other reversible hematologic abnormalities, 
including decreased reticulocyte count, were observed after multiple-dose 
administration of higher dose levels at which JAK2 inhibition was noted. 
 
1.2.3 Clinical Experience With Itacitinib for the Treatment of aGVHD 
 
In a Phase 1 study that assessed the safety and tolerability of itacitinib in 
combination with corticosteroids, 30 aGVHD subjects were randomized to 1 of 2 
treatment cohorts (200 mg cohort, n = 14; 300 mg cohort, n = 16).  One subject was 
randomized to the 200 mg cohort but withdrew from the study before starting 
treatment.  One DLT of Grade 3 thrombocytopenia was reported in 1 subject with 
pre-existing thrombocytopenia who was randomized to the 300 mg cohort.  
Adverse events reported in greater than 20% of all subjects include diarrhea, 
hypokalemia, 
peripheral 
edema, 
hyperglycemia, 
abdominal 
pain, 
hypophosphatemia, 
fatigue, 
headache, 
hypomagnesemia, 
and 
sepsis.  
Thrombocytopenia and platelet count decreases were observed in 24.2% and 20.7% 
of subjects, respectively, with a higher proportion of these events occurring in the 
300 mg cohort, although a higher incidence of pre-existing thrombocytopenia was 
also observed in this group.  The Day 28 ORR in first-line aGVHD subjects in both 
treatment cohorts was 83.3%; for subjects with SR-aGVHD, the overall Day 28 
ORR was 64.7% (200 mg cohort, 62.5%; 300 mg cohort, 66.7%).  Most responses 
occurred within the first 14 days of treatment, and responses were durable, with a 
median DOR of 130 days and 136 days in the 200 mg cohort and 300 mg cohort, 
respectively.  Complete response rates of 66.7% and 17.6% were reported for first-
line and SR-aGVHD cohorts, respectively.  Pharmacokinetics of itacitinib were 
evaluated using plasma samples collected predose and at 1 hour, 2 hours, and 4 to 
8 hours postdose on Study Days 1 and 7.  Although inter-subject variability was 
found to be high, PK exposure (Cmax and AUC) was consistent with historical data, 


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and a large overlap in steady-state exposure was observed between the 200 mg and 
300 mg cohorts.  The higher incidence of thrombocytopenia and DLT of 
thrombocytopenia in the 300 mg cohort, as well as similarities in PK and efficacy 
between dose groups, led to the identification of the 200 mg dose of itacitinib as 
the recommended dose for future GVHD studies (Schroder et al 2016). 
 
1.3 
Study Rationale  
 
In this trial, we will begin to explore the possibility that, as in mice, JAK1 inhibition with 
haplo-HCT may mitigate GVHD and CRS while retaining GVL and improving 
engraftment.  Both preclinical and clinical data (see Sections 1.1.4 and 1.1.5) suggest that 
inhibition of IFNγ and IL-6, directly and using downstream JAK Inhibitors, may be an 
effective strategy to decrease toxicities and improve disease control for patients undergoing 
haplo-HCT.  Itacitinib, as a specific JAK1 inhibitor, may have less deleterious effect on 
engraftment than less specific JAK inhibitors.  The purpose of this pilot study is to 
determine the safety of itacitinib with haplo-HCT measured by the effect on 
engraftment and grade III-IV GVHD. 
 
1.3.1 Rationale for Expansion Phase 
 
The pilot study completed enrollment in one year, and the intervention has proven 
safe with no patients meeting either primary safety endpoints of engraftment failure 
or severe acute GVHD by Day 100.  In fact, of the 19 evaluable patients on study, 
none have been diagnosed with severe acute GVHD or chronic GVHD up to this 
point.  We therefore propose to further study the safety and efficacy of this 
intervention in an extension study of 20 patients.  In addition, we will extend the 
treatment period from 100 days to 180 days to allow tacrolimus tapering to occur 
before itacitanib tapering. In the pilot study, several patients had mild acute GVHD 
during the taper period which responded to resumption of higher dose of itacitanib.  
Furthermore, during the treatment period we observed neutropenia and/or 
thrombocytopenia which responded to growth factor support.  We have therefore 
amended the study to mandate that patients for whom itacitanib is held for 
cytopenias receive growth factors to continue until count recovery and resumption 
of itacitanib or toxicity. 
 
During the study, time to engraftment has been encouraging.  Therefore, the 
original exclusion of patients with myelofibrosis and those whose donors fail to 
collect the target number of CD34+ cells, may be unnecessary.  To examine the 
safety in these populations, we have amended the expansion phase to include: 1) 
Five patients with myelofibrosis, and 2) Three patients whose donors fail to collect 
the target number of CD34+ cells and the treating physician choses to move forward 
with the haplo-HCT. 
 
This extension study will provide more experience using itacitanib in this context 
and form the basis for a large, placebo-controlled, multicenter trial evaluating 
itacitanib for prevention of GVHD and cytokine release syndrome after haplo-HCT. 


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2.0 
OBJECTIVES 
 
2.1 
Pilot Study Objectives 
 
2.1.1 Primary Endpoints  
 
1. To determine the cumulative incidence of graft failure at 35 days post haplo-
HCT. 
2. To determine the cumulative incidence of grade III-IV acute GVHD by Day 
100.  
 
2.1.2 Secondary Endpoints 
 
1. To determine the incidence and grade of CRS. 
2. To determine treatment related mortality at day 180. 
 
2.1.3 Exploratory Endpoints 
 
1. Cumulative incidence of relapse at six months and one year. 
2. Overall survival at 6 months and one year 
3. To determine the cumulative incidence of failure of platelet engraftment 35 
days post haplo-HCT. 
4. GVHD Relapse Free Survival (GRFS) at one year. 
5. Incidence and types of infections within one year.  
6. Cumulative incidence of acute GVHD grade II-IV at Day 180 
7. Cumulative incidence of acute GVHD grades III-IV at Day 180 
8. Cumulative incidence of chronic GVHD at one year post transplant. 
9. Incidence of IL-6 inhibitor therapy. 
10. We will collect annotated patient samples for analysis of cytokines, JAK/STAT 
phosphorylation, and immune reconstitution and look for associations with 
patient outcomes. 
 
2.2 
Expansion Phase Objectives 
 
2.2.1 Primary Endpoint 
 
To determine the cumulative incidence of acute GVHD grades III-IV at Day 100. 
 
2.2.2 Secondary Endpoints 
 
1. To determine the cumulative incidence of acute GVHD grade II-IV at Day 100 
2. To determine the incidence and grade of CRS. 
3. To determine treatment related mortality at day 180. 
 


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2.2.3 Exploratory Endpoints 
 
1. Cumulative incidence of relapse at six months and one year. 
2. Overall survival at 6 months and one year 
3. To determine the cumulative incidence of failure of platelet engraftment 35 
days post haplo-HCT. 
4. GVHD Relapse Free Survival (GRFS) at one year. 
5. Incidence and types of infections within one year.  
6. Cumulative incidence of acute GVHD grade II-IV at Day 180 
7. Cumulative incidence of acute GVHD grades III-IV at Day 180 
8. Cumulative incidence of chronic GVHD at one year post transplant. 
9. Incidence of IL-6 inhibitor therapy. 
10. We will collect annotated patient samples for analysis of cytokines, JAK/STAT 
phosphorylation, and immune reconstitution and look for associations with 
patient outcomes. 
 
 
3.0 
PATIENT SELECTION 
 
3.1 
Inclusion Criteria  
 
Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise 
noted. 
 
1. Diagnosis of a hematological malignancy listed below: 
a. Acute myelogenous leukemia (AML) in complete morphological remission (based 
on IWG Criteria47). 
b. Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD 
negative, based on IWG Criteria47). 
c. Myelodysplastic syndrome with ≤5% blasts in bone marrow. 
d. Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD) in 2nd or greater 
complete or partial remission.  
 
2. Planned treatment is myeloablative or reduced intensity conditioning followed by T 
Cell–replete peripheral blood haploidentical donor transplantation (see Section 6.1).  
 
3. Available HLA-haploidentical donor who meets the following criteria: 
a. Blood-related family member, including (but not limited to) sibling, offspring, 
cousin, nephew, or parent. Younger donors should be prioritized. 
b. At least 18 years of age. 
c. HLA-haploidentical donor/recipient match by at least low-resolution typing per 
institutional standards. 
d. In the investigator’s opinion, is in general good health, and medically able to 
tolerate leukapheresis required for harvesting HSC. 
e. No active hepatitis. 
f. Negative for HTLV and HIV. 


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g. Not pregnant. 
h. Donor selection will be in compliance with FDA guidelines as provided in 21 CFR 
1271 for donor eligibility 
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceR
egulatoryInformation/Guidances/Tissue/UCM091345.pdf 
i. Safety Lead-In Phase: For the first three patients, the donor must consent to a 
second product collection should it prove necessary. 
 
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix 
1). 
  
5. Adequate organ function as defined below: 
a. Total bilirubin must be within normal range at baseline. 
b. AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN. 
c. Creatinine ≤ 1.5 x IULN 
OR 
creatinine clearance ≥ 45 mL/min/1.73 m2 by Cockcroft-Gault Formula. 
d. Oxygen saturation ≥ 90% on room air. 
e. LVEF ≥ 40%. 
f. FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, 
patients will still be considered eligible if deemed safe after a pulmonary evaluation. 
 
6. At least 18 years of age at the time of study registration 
 
7. Able to understand and willing to sign an IRB approved written informed consent 
document (or that of legally authorized representative, if applicable). 
 
8. Must be able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil, 
and cyclophosphamide as outlined in Section 6.2. 
 
3.2 
Exclusion Criteria 
 
 
1. Must not have undergone a prior allogeneic donor (related, unrelated, or cord) 
transplant. Prior autologous transplant is not exclusionary. 
 
2. Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) 
of ≥ 2000 as assessed by the single antigen bead assay. 
 
3. Known HIV or active hepatitis B or C infection. 
 
4. Known hypersensitivity to one or more of the study agents, including ruxolitinib and 
itacitinib.  
 
5. Must not have myelofibrosis (unless they are enrolled Amendment #5 or later, see 
section 3.3) or other disease known to prolong neutrophil engraftment to > 35 days 
after transplant. 


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6. Must not receive antithymocyte globulin as part of pre-transplant conditioning 
regimens. 
  
7. Currently receiving or has received any investigational drugs within the 14 days prior 
to the first dose of study drug (Day -3). 
 
8. Pregnant and/or breastfeeding. 
 
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection, autoimmune disease, symptomatic congestive heart failure, unstable angina 
pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that 
would limit compliance with study requirements.  
 
10. Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency 
will not be excluded. 
 
3.3 
Additional Inclusion Criteria Under Amendment 5 
 
1. Five subjects with myelofibrosis will be enrolled in the expansion phase. 
 
2. Three patients whose donors fail to collect the target number of CD34+ cells and the 
treating physician choses to move forward with the haplo-HCT will be enrolled in the 
exapansion phase. 
 
 
3.4 
Eligibility of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial.  
 
 
4.0 
REGISTRATION PROCEDURES  
 
Patients must not start any protocol intervention prior to registration through the Siteman 
Cancer Center. 
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility 
2. Registration of patient in the Siteman Cancer Center OnCore database 
3. Assignment of unique patient number (UPN) 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed below: 


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1. Registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form  
5. Completed eligibility checklist, signed and dated by a member of the study team 
6. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
All patients must be registered through the Siteman Cancer Center OnCore database. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  All data 
will be recorded with this identification number on the appropriate CRFs. 
 
 
5.0 
TREATMENT PLAN 
 
5.1 
Overall Treatment Plan 
 
For subjects enrolled in the Pilot Study, (prior to Amendment 3), we will administer 
itacitinib 200 mg/day from Day -3 to Day 100, followed by a taper as defined in Section 
6.4.1.  For subjects enrolled in the Expansion Phase (Amendment 3 and later), we will 
administer itacitinib 200 mg/day from Day -3 to Day 180, followed by a taper as 
defined in Section 6.4.1.  In cases of engraftment failure or severe infection, itacitinib will 
be dose modified (see Section 6.4).  Itacitinib can be discontinued by physician discretion 
for toxicities attributable to the drug.  
 
Safety Lead-In Phase (Three Patients): To address concerns of engraftment failure using 
itacitinib throughout the transplant period, for the first three patients we will consent the 
donor for a second CD34+ collection to use as a rescue in the case of engraftment failure 
and for collection of a research blood specimen prior to mobilization (refer to Section 
10.1.3).  If by Day 21 the ANC remains zero, we will start the process to arrange donor 
cell collection.  In the case of engraftment failure at Day 35, itacitinib will be discontinued, 
the donor will undergo apheresis, and product will undergo CD34+ selection per 
institutional standards and infused as soon as possible.  After the first three patients are 
transplanted with an adequate CD34+ dosed product, further enrollment will be held until 
two of the three have achieved engraftment. 
 
5.2 
Evaluability 
 
All patients who receive at least one dose of itacitinib are evaluable for the toxicity 
endpoints.  Patients are evaluated for toxicity from the first dose of itacitinib (Day -3) until 


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30 days after the last dose of itacitinib.  Toxicities will be recorded using the NCI CTCAE 
version 5.0. 
 
All patients who undergo transplant and have received at least one dose of itacitinib are 
evaluable for the engraftment endpoint. 
 
5.3 
Replacement of Ineligible Patients 
 
Should a patient be enrolled and subsequently be unable to start treatment with itacitinib 
on Day -3 as per protocol (due to declining performance status, unacceptable lab results, 
or other reason), the patient will be removed from the study and will be replaced.  Should 
a patient be enrolled and subsequently be unable to undergo stem cell transplant protocol 
(due to declining performance status, unacceptable lab results, or other reason), the patient 
will be removed from the study and will be replaced.  Should a patient be enrolled and 
subsequently not receive goal cell infusion (at least 5 x 106 CD34+ cells/kg (recipient 
weight)), the patient will be removed from the study and will be replaced.  Amendment #5 
adds three slots for patients who do not receive goal cell infusion who will remain on the 
study drug. 
 
Such subjects that receive study drug will be evaluable for treatment related toxicity and 
monitored for 30 days after study drug exposure but will not be evaluable for the safety 
endpoints of engraftment and GVHD. 
 
 
6.0 
ADMINISTRATION OF PROTOCOL TREATMENT 
 
6.1 
Conditioning Regimens for Transplant 
 
Although including myeloablative (MA) and reduced-intensity conditioning (RIC) 
regimens may result in added variability, retrospective studies comparing MA and RIC in 
AML/MDS show similar outcomes of survival, treatment related mortality and GVHD48,49.  
Both types of regimens are being allowed in this protocol to tailor conditioning at the 
discretion of the treating physician and to enhance patient enrollment.  Historically about 
50% of our transplants for AML and MDS are performed using RIC. 
 
Recipients will undergo institutionally standard myeloablative or reduced intensity 
chemotherapy or chemoradiotherapy using one of the following conditioning regimens, 
which will be administered at the discretion of the treating physician: 
 
• Fludarabine + Cyclophosphamide + TBI 
• Fludarabine + Fractionated TBI 
• Fludarabine + Busulfan 2 
• Fludarabine + Busulfan 4 
 


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Anithymocyte globulin will not be permitted as part of pre-transplant conditioning 
regimens in this protocol due to its potential impact on modulating the incidence of GVHD 
or GVL. 
 
6.2 
Standard of Care GVHD Prophylaxis 
 
Tacrolimus, mycophenolate mofetil, and post-transplant cyclophosphamide is the only 
prophylactic GVHD regimen allowed on this trial. 
 
Post-transplant cyclophosphamide will be administered at a dose of 50 mg/kg on Days 3 
and 4. 
 
Tacrolimus will be administered orally at a dose of 0.03 mg/kg or intravenously at a dose 
of 0.03 mg/kg or an initial flat dose of 1mg/day beginning on Day 5 and continue for a 
minimum of 100 days prior to tapering.  Tacrolimus should be titrated to maintain a 
suggested level of 5-15 ng/mL per institutional guidelines.  
 
Mycophenolate mofetil will be administered orally at a dose of 15 mg/kg TID (based upon 
actual body weight) with the maximum total daily dose not to exceed 3 grams (1g TID, IV 
or PO) beginning on Day 5 and continuing until Day 35 then managed per institutional 
guidelines. 
 
6.3 
Stem Cell Transplantation (Day 0)  
 
On Day 0 the allograft will be infused per standard institutional practice.  In the event that 
less than 5.0 x 106 CD34+ cells/kg are infused, the recipient will be removed from the trial 
and replaced.  If study drug has already been administered, it will be discontinued and the 
patient will be followed for toxicity endpoints but not engraftment and GVHD.  This is to 
ensure consistency in the donor product cell count as this may independently affect 
incidence of engraftment and GVHD. Amendment #5 adds three slots for patients who do 
not receive goal cell infusion who will remain on the study drug.   
 
6.4 
Itacitinib  
 
6.4.1 Administration 
 
Pilot Study (enrolled prior to Amendment 3) 
 
Itacitinib will be administered PO at a starting dose of 200 mg QD (2 × 100 mg 
tablets) from Day -3 to Day 100.   
 
- 
After Day 100, for patients at a dose of 200 mg daily, reduce itacitinib to 100 
mg daily for one month, then every other day for one month, then discontinue.   
 
OR 
 


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- 
After Day 100, for patients already dose reduced to 100 mg daily, reduce 
itacitinib to 100 mg every other day then discontinue.  
 
OR 
 
- 
After Day 100, for patients on study drug hold, discontinue permanently.  
 
Itacitinib may be taken without regard to food. 
 
Expansion Phase (enrolled in Amendment 3 or later) 
 
Itacitinib will be administered PO at a starting dose of 200 mg QD (2 × 100 mg 
tablets) from Day -3 to Day 180.   
 
- 
After Day 180, for patients at a dose of 200 mg daily, reduce itacitinib to 100 
mg daily for one month, then every other day for one month, then discontinue.   
 
OR 
 
- 
After Day 180, for patients already dose reduced to 100 mg daily, reduce 
itacitinib to 100 mg every other day then discontinue.  
 
OR 
 
- 
After Day 180, for patients on study drug hold, discontinue permanently.  
 
Itacitinib may be taken without regard to food. 
 
6.4.1.1 Taper Period, Further Guidance 
 
Tapering of other immunosuppressive agents – such a tacrolimus or 
mycophenolate mophetil – should be avoided during the itacitinib taper if 
possible. 
 
If patients develop new GVHD, or worsening of existing GVHD during 
itacitinib taper period, then itacitinib should be increased one dose level 
and taper discussed with principal investigator.  The taper may be done 
more slowly or in the presence of an adjunct immunosuppressive agent. 
 
6.4.2 Itacitinib Dose Modifications 
 
 
Treatment with itacitinib may be held up to 14 days to allow for resolution of 
toxicity. Subjects may resume treatment if no medical condition or other 
circumstance exists that, in the opinion of the investigator, would make the subject 
unsuitable for further participation in the study.  The investigator should contact the 
PI medical monitor to discuss cases where treatment has been delayed for more 


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than 14 days before restarting treatment. 
 
 
Dose reductions are mandated per Table 1 and Table 2. 
 
 
Subjects receiving itacitinib at a dose of 200 mg QD may have their dose reduced 
to 100 mg QD.  Subjects who are unable to tolerate itacitinib at a dose of 100 mg 
QD should be withdrawn from study treatment. 
 
 
Table 1: Dose Interruption and Restarting of Itacitinib 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
• AST and/or ALT > 3.0 × ULN in 
subjects with normal ALT/AST at 
baseline that is not clearly and 
solely related to an extraneous 
cause. 
Day 1-35:  Monitor; no modification required. 
Day 35 – EOT:  
• Interrupt for up to 14 days until the toxicity has resolved 
to ≤ Grade 1.  Exceptions require PI approval.   
• Restart if Grade 3, restart at next lower dose and monitor 
as clinically indicated. 
• Discontinue if Grade 4 unless an exception is made with 
PI approval. 
• Triglycerides >500 mg/dL - 1000 
mg/dL; >5.7 mmol/L - 11.4 
mmol/L, Grade 3 
Hypertriglyceridemia 
• Continue treatment and manage the toxicity. 
• Monitor as clinically indicated. 
• Triglycerides >1000 mg/dL; >11.4 
mmol/L; life-threatening 
consequences, Grade 4 
Hypertriglyceridemia 
Day 0 – EOT:  
• Interrupt for up to 14 days until the toxicity has resolved 
to ≤ Grade 2.  Exceptions require PI approval.   
• Restart at next lower dose and monitor as clinically 
indicated. 
 
Hematology 
• ANC < 1.0 × 109/L 
Day -3 - 35:  Monitor; no modification required. 
Day 35 – EOT:  
• 
Initiate growth factor support and continue until ANC is ≥ 
1 × 109/L for more than 7 days or treating physician feels 
risk outweighs benefit.  
• Monitor ANC count as clinically indicated.  
• ANC < 0.5 × 109/L 
Day -3 - 35:  Monitor; no modification required. 
Day 35 – EOT:  
• Interrupt for up to 14 days until ANC returns to ≥ 0.5 × 
109/L for more than 3 days. Initiate growth factor 


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ADVERSE EVENT 
ACTION TAKEN 
support and continue until itacitanib back to full dose 
or treating physician feels risk outweighs benefit.  
• Reduce dose by 1 dose level. 
• Monitor ANC count as clinically indicated.  
• Resume previous dose if ANC count is ≥ 0.5 × 109/L for 
more than 7 days. 
• Engraftment failure at Day 35 
Discontinue itacitinib. 
 
Donor will undergo apheresis and product will undero CD34+ 
selection per institutional standards and be infused as soon as 
possible. 
• Platelet count is < 25 × 109/L, 
Grade 4 Thrombocytopenia  
Day -3 – Platelet Engraftment:  Monitor; no modification 
required. 
Day 35 – EOT:  
• Interrupt for up to 14 days until platelet count returns to 
≥ 25 × 109/L for more than 3 days.  Initiate growth factor 
support and continue until itacitanib back to full dose or 
treating physician feels risk outweighs benefit. 
• Reduce dose by 1 level upon recovery of platelets 
≥ 25 × 109/L  
• Monitor platelet count as clinically indicated.  
• Resume at previous dose if platelet count remains 
≥ 25 × 109/L for more than 7 days at reduced dose. 
• Platelet count drops by 50% after 
engraftment with a peak platelet 
count ≥ 100 × 109/L on two 
consecutive hemograms, and 
platelet count is < 50 × 109/L, and 
believed related to study 
medication. 
• Interrupt for up to 14 days until platelet count returns to 
≥ 100 × 109/L for more than 3 days. Consider growth 
factor support. 
• Reduce dose by 1 dose level if assessed to be related to 
itacitinib. 
• Monitor platelet count as clinically indicated. 
• Resume at previous dose if platelet count returns to 
≥ 100 × 109/L for more than 7 days. 
Other toxicities 
• Any Grade 1 or Grade 2 toxicity. 
• Continue treatment and manage the toxicity. 
• Monitor as clinically indicated. 
• Major bleeding defined as:  
1. Intracranial bleeding.  
2. Hemoglobin decrease ≥ 2 g/dL 
due to bleeding.  
• Interrupt for up to 14 days until bleeding has resolved. 
• Reduce dose by 1 dose level if assessed to be related to 
itacitinib. 
• Resume at previous dose if bleeding resolves.  
• Any other non-hematologic Grade ≥ 
3 organ toxicity not clearly and 
solely related to extraneous cause. 
• Interrupt up to 14 days until toxicity resolves to ≤ Grade 
1. 
• Restart at reduced dose level for grade 3.  Discontinue 
study drug permanently for grade 4 toxicities. 
• Any other recurrent Grade 3 
toxicity attributable to study drug at 
100 mg QD dose. 
• Discontinue study treatment; follow-up per Protocol.  
Exceptions require sponsor approval. 


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Page 28 of 81 
ADVERSE EVENT 
ACTION TAKEN 
• Any other Grade 4 toxicity 
attributable to study drug. 
• Discontinue study treatment; follow-up per Protocol. 
• Severe infection (Grade 4: life 
threatening consequences) 
• Discontinue study treatment; follow-up per Protocol. 
• Secondary graft failure 
• Discontinue study treatment; follow-up per Protocol. 
ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; CMV = 
cytomegalovirus; ULN = upper limit of normal. 
 
Table 2: Dose Reduction Levels for Itacitinib 
Current Dose 
First Dose Reduction 
Second Dose Reduction 
200 mg QD 
100 mg QD 
Discontinue 
 
6.4.2.1 Excessive Toxicity and Early Treatment Termination 
 
In addition to the above dose modifications (section 6.4.2), itacitinib must 
be discontinued for any of the following reasons: 
• Failure to engraft at Day 35 
• Relapse of the patient’s primary diagnosis  
• Development of steroid refractory acute GVHD 
• Any grade 4 organ toxicity that is not clearly and solely due to an 
extraneous cause  
• A two week or greater delay in study drug administration that is due to 
toxicity. 
• Suspected pregnancy  
• Serious noncompliance with the study protocol 
• Lost to follow-up 
• Patient withdraws consent 
• The PI decides to remove the recipient from study 
• The Siteman Cancer Center decides to close the study 
• Adverse event(s) that, in the judgment of the Investigator, may cause 
severe or permanent harm or which rule out continuation of study drug. 
• General or specific changes in the recipient’s condition rendering 
him/her unacceptable for further treatment in the judgment of the 
investigator 
 
6.5 
General Concomitant Medication and Supportive Care Guidelines 
 
Concomitant medications and supportive care measures will be given per institutional 
guidelines and at the discretion of the treating physician whenever medically necessary 
with the exceptions of the prohibited medications listed in Section 6.6. 
 
6.6 
Prohibited Medications 
 


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The following medications are prohibited during the treatment period of the study: 
 
• Conditioning regimen agents other than those specified in this protocol. 
 
• Concomitant use of another JAK inhibitor. 
• All prophylactic medications for GVHD other than those specified in this protocol.  
The use of corticosteroids for reasons other than GVHD prophylaxis will be 
permitted with documentation of the rationale for usage. 
• Initiating therapy with an investigational medication. 
 
6.7 
Women of Childbearing Potential 
 
Women of childbearing potential (defined as women with regular menses, women with 
amenorrhea, women with irregular cycles, women using a contraceptive method that 
precludes withdrawal bleeding, and women who have had a tubal ligation) are required to 
have a negative pregnancy test prior to initiating the conditioning regimen.   
 
Female and male patients (along with their female partners) are required to use two forms 
of acceptable contraception, including one barrier method, during participation in the study 
and for one month following the last dose of study drug. 
  
6.8 
Treatment of Acute GVHD 
 
In the event that a subject develops acute GVHD the following steps will be taken: 
 
1. Study drug will continued.  
2. Acute GVHD will be treated per the standard of care with high dose steroids. 
3. If steroid refractory GVHD develops, study drug will be discontinued 
 
6.9 
Failure to Engraft 
 
Failure to engraft will be defined as failure to achieve absolute neutrophil count > 500 for 
3 days by Day 35.  At this time, study drug will be discontinued and a bone marrow biopsy 
and chimerism analysis will be performed.  If this occurs during the safety lead in phase, 
rescue product will be administered.  Otherwise, engraftment failure will be managed at 
the discretion of the treating physician. 
 
6.10 
Duration of Therapy 
 
In the Pilot Study (prior to Amendment 3) treatment with itacitinib may continue from 
haplo-HCT Day -3 to Day 100 followed by a taper as defined in Section 6.4.1. In the 
Expansion phase (Amendment 3 or later) treatment with itacitinib may continue from 
haplo-HCT Day -3 to Day 180 followed by a taper as defined in Section 6.4.1.  In cases 
of engraftment failure or severe infection, itacitinib will be dose modified (see Section 6.4).  
Study drug will be discontinued for toxicities attributable to the drug, including: 
• Failure to engraft at Day 35 
• Relapse of the patient’s primary diagnosis  


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• Development of steroid refractory acute GVHD 
• Adverse event(s) that, in the judgment of the Investigator, may cause severe or 
permanent harm or which rule out continuation of study drug. 
• Any grade 4 organ toxicity that is at least possibly related to itacitinib 
• A two week or greater delay in study drug administration that is due to toxicity. 
• General or specific changes in the recipient’s condition rendering him/her 
unacceptable for further treatment in the judgment of the investigator 
• Suspected pregnancy  
• Serious noncompliance with the study protocol 
• Lost to follow-up 
• Patient withdraws consent 
• The PI decides to remove the recipient from study 
• The Siteman Cancer Center decides to close the study 
 
6.11 
Post-Treatment Follow-Up 
 
Patients will be followed for 1 year after first dose of study drug. Patients who prematurely 
discontinue treatment should still complete the remaining study visits (if willing and able).  
 
6.12 
End of Study Definition 
 
The end of study is defined as any one of the following (whichever occurs first): 
•  The date of the one-year follow-up 
•   The date of death 
• Lost to follow-up 
• Patient withdraws consent 
• Relapse 
• Investigator Discretion 
 
6.13 
Definition of Completed Patients 
 
A completed patient is one who receives treatment and completes the one year follow-up 
visit. 
 
 
7.0 
PHARMACEUTICAL INFORMATION  
 
7.1 
Itacitinib 
 
7.1.1 Mechanism of Action/Classification  
 
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. Itacitinib is an investigational product 
that is proposed for development for treatment of myeloproliferative neoplasms 
(MPNs), including myelofibrosis (MF); inflammatory diseases, including 


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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. 
 
7.1.2 Pharmacodynamics/kinetics 
 
Itacitinib potently inhibits JAK1 (half maximal inhibitory concentration [IC50] = 
3.6 nM at 1 mM adenosine triphosphate concentration), with 22- to > 500-fold 
selectivity over the other JAK family members, JAK2, JAK3, and TYK2. It does 
not significantly inhibit (< 30% inhibition) a broad panel of approximately 60 other 
kinases. Itacitinib is also potent (IC50 values of approximately 10 nM to 350 nM) 
in cytokine-driven cell-based assays. This effect is not due to general cytotoxicity. 
Itacitinib also inhibits the growth of the cytokine-dependent cell line INA-6. 
Itacitinib potently inhibits the phosphorylation of signal transducer and activator of 
transcription (STAT) proteins and the production of proinflammatory factors 
induced by other cytokines, such as interleukin (IL)-23 and IL-6 with IC50 values 
of approximately 30 nM to 100 nM. In contrast, itacitinib shows less inhibition in 
cell-based assays dependent on JAK2 with IC50 values of approximately 1 μM 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 (WT) JAKs when administered by continuous 
infusion, achieving plasma concentrations well below those necessary to inhibit 
JAK2. Oral itacitinib also reduced splenomegaly in a model of JAK2 V617F-driven 
neoplasia relevant to MF. 
 
7.1.3 Formulations 
 
Itacitinib may be formulated as 25 mg, 100 mg, 200 mg, or 300 mg (free base 
equivalent) SR tablets. These tablets contain the active ingredient, hypromellose, 
microcrystalline cellulose, lactose monohydrate, and magnesium stearate, and may 
be coated with a nonfunctional coating. 
 
Itacitinib may also be formulated as 100 mg or 300 mg (free base equivalent) IR 
tablets. These tablets contain the active ingredient, microcrystalline cellulose, 
lactose monohydrate, pregelatinized starch, hydroxypropyl cellulose, sodium starch 
glycolate, and magnesium stearate. 
 
7.1.4 Supply, Packaging, and Labeling  
 
Itacitinib tablets will be provided to sites in high-density polyethylene bottles as 
applicable by Incyte.  No preparation is required.  All Incyte investigational product 


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labels will be in the local language and will comply with the legal requirements of 
each country. 
 
7.1.5 Storage 
 
Itacitinib should be stored at ambient conditions (15°C to 30°C, or 59°F to 86°F) 
as per the IB. 
 
7.1.6 Administration  
 
Itacitinib will be administered PO at a starting dose of 200 mg QD (2 × 100 mg 
tablets).  Itacitinib may be taken without regard to food. It should be taken at the 
same time every day.  
 
7.1.7 Instruction to Subjects for Handling Itacitinib 
 
 
The subject must be instructed in the handling of itacitinib as follows: 
 
 
• To store the bottles at room temperature, in a safe place and out of the reach 
of children. 
 
• To only remove the number of tablets needed at the time of administration. 
• Not to remove tablets in advance of the next scheduled administration. 
 
• To make every effort to take doses on schedule. 
 
• To report any missed doses.  
• To take tablets with a glass of water.  
• Not to take another dose if vomiting occurs after taking study medication.  
• To bring all used and unused bottles of study medication to the site at each 
visit.  


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Page 33 of 81 
 
8.0 STUDY CALENDAR 
8.1 
Pilot Study 
 
Screening1  PC13 
Day  
-3 
Day 
0 
Day 
3 
Day   
14 
Day 
214 
Day 
284 
Day 
354 
Day 
424 
Day 
604 
Day 
744 
Day 
1004 
Taper Period  
Days 101-160 
End of 
Treatment17 
Follow Up 
Period – 
Monthly 
Visits12 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Itacitinib Oral2 
 
 
Continuous Dosing 
Taper. 
 
 
Engraftment Assessment 
 
 
 
 
 
 
X9 
 
 
 
 
 
 
 
 
 
Physical exam and ROS 
X 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X15 
 
X16 
ECOG PS  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
X 
Adverse Event assessment 
 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Acute GVHD assessment5 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X15 
 
X16 
Chronic GVHD assessment 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X15 
 
X16 
CRS grading 
 
 
X 
Daily 
X 
X 
 
 
 
 
 
 
 
 
Immunosuppressive Medication 
Questionnaire 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
X16 
 
X16 
FACT-BMT and HAP 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
X15 
 
X19 
CBC with diff  
X 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Na, K, Cl, Creat, BUN 
X 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Bili, ALT, AST, Alk Phos 
X 
 
Weekly 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
CRP and ferritin 
 
 
Days -1, 0, 2, 4, 6, 8, 10, 12, 14 
 
 
 
 
 
 
 
 
 
 
Lipid Panel 
X 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
 
Pregnancy test7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Donor specific anti-HLA Abs 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virology screen2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow biopsy 
X 
 
 
 
 
 
 
X 
X8 
 
 
 
X 
Day 180 
 
 
ECHO or MUGA 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DLCO 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chimerism analysis6 
X 
 
 
 
 
 
 
X 
X8 
 
X 
 
X 
Day 180 
 
X14 
Cytokine Analysis 
 
X 
 
X11 
 
X 
 
 
X 
 
X 
X18 
X 
 
Mass Cytometry Analysis 
 
X 
 
X11 
 
X 
 
 
X 
 
X 
X18 
X 
 
Single Cell RNA Sequencing and 
Whole Serum RNA Expression 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X18 
X 
 
Immune reconstitution analysis 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
X18 
X 
 
GVHD Biomarker Panel 
 
 
 
Day 7 and day of diagnosis of acute GVHD11. 
 
 
1: Screening assessments should occur within 30 days prior to registration, except as noted in Section 9.1 
2: Itacitinib will be administered orally at a dose of 200 mg daily, continuously from Day -3 to day 100 followed by a taper as 
defined in Section 6.4.1.  
3: Donor- HTLV, HIV and hepatitis panel; Recipient- HIV and hepatitis panel  
4: +/- 3 days 
5: Assessment every 1-2 weeks through Day 100. After Day 100, every 4 - 6 weeks (+/- 7 days) through Day 160. 
6: STR on marrow and peripheral split blood chimerism. 
7: For women of childbearing potential only. 
8: Only perform in the case of engraftment failure. 
9: First three patients only. 
10: To be drawn within three days of the diagnosis of acute GVHD. 
11: Days Pre-Conditioning (PC), -1, 3 (pre-cyclophosphamide), 7 (+/- 1), 14 (+/- 1), and Time of Diagnosis of GVHD 
12: Follow up period to last until day 365.  
13: Pre-Conditioning (PC): Blood to be drawn on the first day of conditioning, prior to chemotherapy or radiation. 
14: Chimerism analysis at one year +/- 30 days. 
15: Physical exam, Acute GVHD assessment Chronic GVHD assessment, and Immunosuppressive medication questionnaire 
every two weeks until day 180. 
16: Physical exam, Acute GVHD assessment Chronic GVHD assessment, and Immunosuppressive medication questionnaire 
every month until end of study. 
17: Between 14 and 35 days after the last dose of study drug. 
18: Day 130 +/- 7 days. 
19: FACT-BMT and HAP every two months until end of study. 
 
 
 
 


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8.2 
Expansion Study 
 
Screening1  
PC13 
Day  
-3 
Day 
0 
Day 
3 
Day   
14 
Day 
214 
Day 
284 
Day 
354 
Day 
424 
Day 
604 
Day 
744 
Day 
1004 
Day 
1284 
Day 
1564 
Day 
1804 
Taper 
Period  
Days 
181-240 
End of 
Treatment16 
Follow Up 
Period – 
Monthly 
Visits12 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Itacitinib Oral2 
 
 
Continuous Dosing 
Taper. 
 
 
 
Engraftment Assessment 
 
 
 
 
 
 
X9 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam and ROS 
X 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
ECOG PS  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
 
X 
Adverse Event assessment 
 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Acute GVHD assessment5 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X15 
Chronic GVHD assessment 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
 
X15 
CRS grading 
 
 
X 
Daily 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Immunosuppressive Medication 
Questionnaire 
 
 
 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X15 
 
X15 
FACT-BMT and HAP 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X18 
CBC with diff  
X 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Na, K, Cl, Creat, BUN 
X 
 
Daily 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Bili, ALT, AST, Alk Phos 
X 
 
Weekly 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
CRP and ferritin 
 
 
Days -, 0, 2, 4, 6, 8, 10, 12, 14 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid Panel 
X 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
Pregnancy test7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Donor specific anti-HLA Abs 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virology screen2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow biopsy 
X 
 
 
 
 
 
 
X 
X8 
 
 
 
X 
 
 
X 
 
 
 
ECHO or MUGA 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DLCO 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chimerism analysis6 
X 
 
 
 
 
 
 
X 
X8 
 
X 
 
X 
 
 
X 
 
 
X14 
Cytokine Analysis 
 
X 
 
X11 
 
X 
 
 
X 
 
X 
 
 
X 
X17 
X 
 
Mass Cytometry Analysis 
 
X 
 
X11 
 
X 
 
 
X 
 
X 
 
 
X 
X17 
X 
 
Single Cell RNA Sequencing and 
Whole Serum RNA Expression 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
X17 
X 
 
Immune reconstitution analysis 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
X17 
X 
 
GVHD Biomarker Panel 
 
 
 
 
 
 
Day 7 and day of diagnosis of acute GVHD11. 
 
 
1: Screening assessments should occur within 30 days prior to registration, except as noted 
in Section 9.1 
2: Itacitinib will be administered orally at a dose of 200 mg daily, continuously from Day -
3 to day 180 followed by a taper as defined in Section 6.4.1.  
3: Donor- HTLV, HIV and hepatitis panel; Recipient- HIV and hepatitis panel  
4: +/- 3 days 
5: Assessment every 1-2 weeks through Day 100. After Day 100, every 4 - 6 weeks (+/- 7 
days) through Day 240. 
6: STR on marrow and peripheral split blood chimerism. 
7: For women of childbearing potential only. 
8: Only perform in the case of engraftment failure. 
9: First three patients only. 
10: To be drawn within three days of the diagnosis of acute GVHD. 
11: Days Pre-Conditioning (PC), 3 (pre-cyclophosphamide), 7 (+/- 1), 14 (+/- 1), and Time 
of Diagnosis of GVHD 
12: Follow up period to last until day 365.  
13: Pre-Conditioning (PC): Blood to be drawn on the first day of conditioning, prior to 
chemotherapy or radiation. 
14: Chimerism analysis at one year +/- 30 days. 
15: Physical exam, Acute GVHD assessment Chronic GVHD assessment, and 
Immunosuppressive medication questionnaire every month until end of study. 
16: Between 14 and 35 days after the last dose of study drug. 
17: Correlative sample blood draw Day 210 +/- 7 days. 
18: FACT-BMT and HAP every two months until end of study.


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9.0 
SCHEDULE OF ASSESSMENTS 
 
9.1 
Screening 
 
Within 30 days prior to registration (except where noted) the patient will undergo screening 
assessments as follows: 
• Physical exam and review of systems (ROS) 
• ECOG performance status 
• Quality of Life assessments 
• Complete blood count (CBC) with differential and platelet count 
• Complete metabolic panel (CMP): sodium, potassium, chloride, bicarbonate, blood 
urea nitrogen (BUN), creatinine, glucose, calcium, total protein, albumin, total 
bilirubin, AST, ALT, alkaline phosphatase, lipid panel. 
• Pregnancy test for female patients of childbearing potential (serum or urine) 
• Virology screen (HIV 1 and 2 and hepatitis B and C) (within 60 days) 
• HLA and chimerism analysis 
• Bone marrow aspirate and biopsy (within 60 days) 
• Disease-specific staging (within 60 days) 
• ECHO or MUGA (within 90 days) 
• DLCO (within 90 days) 
 
9.2 
Treatment Schedule and Assessments 
 
9.2.1 Pilot Study  
 
Itacitinib will be administered PO at a starting dose of 200 mg QD (2 × 100 mg 
tablets) from Day -3 to Day 100.  After Day 100, itacitinib will be tapered as 
outlined in Section 6.4.1.  If a patient discontinues treatment, all other 
labs/procedures and assessments should still be completed. 
 
Pre-Conditioning 
• Cytokine Analysis   
• Single Cell RNA Sequencing and Whole Serum RNA Expression  
• Mass Cytometry Analysis 
• Immune reconstitution analysis 
  
Day -3 to Day +14  
• Daily physical exam and ROS 
• Daily CBC with diff, Na, K, Cl, Creat, BUN 
• Weekly Bili, ALT, AST, Alk Phos 
• Daily adverse event assessment. 
• Daily Days 0 to 14: CRS grading 
• Days -1, 3 (prior to cyclophosphamide), 7 (+/- 1), and 14 (+/-1): 
 
• Cytokine Analysis  
 
• Mass Cytometry Analysis  
• Days -1, 0, 2, 4, 6, 8, 10, 12, and 14: CRP and ferritin 


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• Day 3: Single Cell RNA Sequencing and Whole Serum RNA Expression  
• Day 7: GVHD Biomarker Panel 
• Day 14: Acute GVHD assessment 
• Day 14: Immunosuppressive Medication Questionnaire 
• Day 14: Quality of Life assessments 
 
Day 21 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CRS grading 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
• Engraftment assessment (first three patients only).  If ANC is 0, process for 
collection of rescue product will be initiated. 
 
Day 28 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CRS grading 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
• Bone marrow biopsy - MRD testing required if in morphologic CR. 
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Day 35 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• If failure to engraft: 
• Bone marrow biopsy - MRD testing required if in morphologic CR  
• Chimerism Analysis 
 
Day 42 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 


Version 06/01/23 
 
Page 37 of 81 
 
Day 60 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Day 74 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
 
Day 100 (+/- 3 days) 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Bone marrow biopsy - MRD testing required if in morphologic CR  
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Taper Period Days 101-160 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Cytokine Analysis  


Version 06/01/23 
 
Page 38 of 81 
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Post Treatment (Between 14 and 35 days after the last dose of study drug) 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
 
 
Day 180 
• Bone marrow biopsy 
• Chimerism analysis 
 
Follow Up Period – Through Day 365. 
• Monthly visits. 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
 
Within Three Days of Acute GVHD Diagnosis 
• GVHD Biomarker Panel  
 
9.2.2 Expansion Study 
 
Itacitinib will be administered PO at a starting dose of 200 mg QD (2 × 100 mg 
tablets) from Day -3 to Day 180.  After Day 180, itacitinib will be tapered as 
outlined in Section 6.4.1.  If a patient discontinues treatment, all other 
labs/procedures and assessments should still be completed. 
 
Pre-Conditioning 
• Cytokine Analysis   
• Single Cell RNA Sequencing and Whole Serum RNA Expression  
• Mass Cytometry Analysis 
• Immune reconstitution analysis 
  
Day -3 to Day +14  
• Daily physical exam and ROS 
• Daily CBC with diff, Na, K, Cl, Creat, BUN 
• Weekly Bili, ALT, AST, Alk Phos 
• Daily adverse event assessment. 
• Daily Days 0 to 14: CRS grading 


Version 06/01/23 
 
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• Days -, 3 (prior to cyclophosphamide), 7 (+/- 1), and 14 (+/-1): 
 
• Cytokine Analysis  
 
• Mass Cytometry Analysis  
• Days , 0, 2, 4, 6, 8, 10, 12, and 14: CRP and ferritin 
• Day 3: Single Cell RNA Sequencing and Whole Serum RNA Expression  
• Day 7: GVHD Biomarker Panel 
• Day 14: Acute GVHD assessment 
• Day 14: Immunosuppressive Medication Questionnaire 
• Day 14: Quality of Life assessments 
 
Day 21 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CRS grading 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
• Engraftment assessment (first three patients only).  If ANC is 0, process for 
collection of rescue product will be initiated. 
 
Day 28 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CRS grading 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
• Bone marrow biopsy - MRD testing required if in morphologic CR. 
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Day 35 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• If failure to engraft: 
• Bone marrow biopsy - MRD testing required if in morphologic CR  
• Chimerism Analysis 
 
Day 42 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 


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• Acute GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
 
Day 60 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Day 74 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
 
Day 100 (+/- 3 days) 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Bone marrow biopsy - MRD testing required if in morphologic CR  
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Day 128 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 


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• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
 
Day 156 (+/- 3 days) 
• Physical exam and ROS 
• Adverse event assessment. 
• Acute GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos 
 
Day 180 (+/- 3 days) 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Bone marrow biopsy - MRD testing required if in morphologic CR  
• Chimerism Analysis 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Taper Period Days 180-240 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• CBC with diff, Na, K, Cl, Creat, BUN, Bili, ALT, AST, Alk Phos, lipid panel. 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 
Post Treatment (Between 14 and 35 days after the last dose of study drug) 
• Cytokine Analysis  
• Single Cell RNA Sequencing and Whole Serum RNA Expression 
• Mass Cytometry Analysis  
• Immune reconstitution analysis 
 


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Follow Up Period – Through Day 365. 
• Monthly visits. 
• Physical exam and ROS 
• ECOG Performance Status 
• Adverse event assessment. 
• Acute GVHD assessment 
• Chronic GVHD assessment 
• Immunosuppressive Medication Questionnaire 
• Quality of Life assessments 
• Chimerism analysis 
 
Within Three Days of Acute GVHD Diagnosis 
• GVHD Biomarker Panel  
 
 
10.0 
CORRELATIVE STUDIES 
 
10.1 
Correlative Studies Background 
  
10.1.1 Cytokine expression 
 
To determine the effect of itacitinib on cytokine expression, and to correlate this 
with clinical outcomes, we will measure cytokine expression at multiple time points.  
This analysis will yield serial cytokine profiles throughout the transplant period, 
allowing us to compare cytokine profiles serially within the same patient. 
 
10.1.2 JAK and STAT Phosphorylation Analysis by Mass Cytometry  
 
We will measure JAK and STAT phosphorylation at multiple time points.  We aim 
to measure the in vivo effects of the JAK inhibitor, Itacitinib throughout the 
transplant period.  JAK inhibitors have dose dependents effects on various JAKs, 
and there is a certain level of promiscuity in both JAK and STAT functions on 
downstream targets.  This analysis will help elucidate the true effects of itacitinib 
in vivo in patients undergoing haplo-HCT. 
 
10.1.3 Single Cell RNA Sequencing, Whole Serum RNA Expression, and 
Whole Exome Sequencing 
 
We will perform single cell RNA sequencing in a select number of patients in order 
to measure the in vivo effects of Itacitinib on RNA expression. Whole serum RNA 
expression analysis will be performed at the same time points. By analyzing this 
against the single cell RNA expression data, we aim to determine which cell subsets 
are driving overall expression. Whole exome sequencing analysis will be 
performed at baseline on each donor and recipient pair, and data will be used to 
reliable differentiate donor from recipient cells after haplo-HCT. 
 


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Donors who do not sign a consent for this study (because they are not one of the 
donors for the first 3 recipients enrolled) will have specimens collected under 
HRPO# 201103349. 
 
10.1.4 Immune Reconstitution after Transplantation 
 
Immune reconstitution after transplantation is an important determinate for risk of 
infection and GVHD. To understand the kinetics of immune reconstitution after 
transplantation with a mobilized peripheral blood stem cell product with 
administration of itacitinib, we will collect peripheral blood samples at multiple 
time points.   
 
10.1.5 GVHD Biomarker Panel 
 
A serum biomarker panel for the diagnosis and prognostication in GVHD would 
represent a clinically important development for patients undergoing stem cell 
transplantation (see Section 1.1.2.2).  These tools have not been validated either in 
the haplo-HCT settings or in the setting of JAK inhibition.  We will draw a broad 
plasma biomarker panel on Day 7 and within three days of the diagnosis of acute 
GVHD.   
 
10.1.6 Sample Delivery 
 
Samples must be maintained at room temperature and delivered as soon as possible 
to the Tissue Procurement Core at Siteman Cancer Center, BJC-Institute of Health, 
Room 5113, 425 S. Euclid Ave., St. Louis, MO 63110, 314-454-7605. Specimens 
will be identified by patient specific number and study number.  
 
10.1.7 Sample Processing 
 
All samples will be frozen and batch run.  Please refer to laboratory manual for 
sample processing details. 
 
10.1.8 Correlative Sample Blood Volume 
 
Total blood volume drawn for correlative samples will be between 20-75 mL for 
each time point. 
 
10.2 
Questionnaires  
 
10.2.1 Pilot Study 
 
10.2.1.1 
GVHD Assessments 
 
Acute GVHD will be assessed using MAGIC criteria (Appendix 2).  
Chronic GVHD will be accessed using the NIH consensus criteria 
(Appendix 3).  Acute GVHD will be assessed on Days 14, 21, 28, 35, 42, 


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60, 74, 100, Taper Period, and Follow-Up Period.  Chronic GVHD will be 
assessed on Day 100, Taper Period, and Follow-Up Period. 
 
10.2.1.2 
Quality of Life Assessments  
 
Quality of Life (QOL) will be assessed by a patient self-report questionnaire 
FACT-BMT and Human Activity Profile (HAP) (Appendices 4 and 5). 
QOL questionnaires will be completed on Screening, Days 14, 28, 42, 100, 
Taper Period, and Follow-Up Period. 
 
10.2.1.3 
Immunosuppressive Medication Questionnaire 
 
The use of immunosuppressive medications will be captured using the 
Immunosuppressive Medication Questionnaire (Appendix 6) on Days 14, 
28, 42, 74, 100, Taper Period, and Follow-Up Period. 
 
10.2.2 Expansion Phase 
 
10.2.2.1 
GVHD Assessments 
 
Acute GVHD will be assessed using MAGIC criteria (Appendix 2).  
Chronic GVHD will be accessed using the NIH consensus criteria 
(Appendix 3).  Acute GVHD will be assessed on Days 14, 21, 28, 35, 42, 
60, 74, 100, 128, 156, 180, Taper Period, and Follow-Up Period.  Chronic 
GVHD will be assessed on Day 100, 180, Taper Period, and Follow-Up 
Period. 
 
10.2.2.2 
Quality of Life Assessments  
 
Quality of Life (QOL) will be assessed by a patient self-report questionnaire 
FACT-BMT and Human Activity Profile (HAP) (Appendices 4 and 5). 
QOL questionnaires will be completed on Screening, Days 14, 28, 42, 100, 
128, 156, 180, Taper Period, and Follow-Up Period. 
 
10.2.2.3 
Immunosuppressive Medication Questionnaire 
 
The use of immunosuppressive medications will be captured using the 
Immunosuppressive Medication Questionnaire (Appendix 6) on Days 14, 
28, 42, 74, 100, 128, 156, 180, Taper Period, and Follow-Up Period. 
 
 
11.0 
DATA SUBMISSION SCHEDULE 
 
Case report forms will be completed according to the schedule listed in this section.  There is a 
window of up to 14 days allowed between the time point listed in the submission schedule and the 
date when the form must be completed. 


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11.1 
Pilot Study 
 
Case Report Form 
Submission Schedule 
Consent form 
Prior to starting treatment 
On Study 
Medical and Surgical History 
Treatment History 
Baseline 
CBC 
Screening, Days -3, 0-14, 21, 28, 35, 42, 60, 74, 100, end of 
itacitinib taper, monthly during follow-up 
Chimerism 
Screening, Day 28, Day 35 (if applicable), Day 60, Day 100, 
end of taper period 
Correlative Studies  
Days -1, 3, 7, 14, 28, and 100 
Response Assessment  
Baseline and Day 28 (and Day 35 if applicable) 
FACT-BMT 
Human Activity Profile 1 of 2 
Human Activity Profile 2 of 2 
Baseline, Days 14, 28, 42, 74, 100, once during taper period, 
monthly during follow-up 
End of Treatment 
End of treatment 
Acute GVHD Assessment 
Days 14, 21, 28, 35, 42, 60, 100, and end of itacitinib taper. 
Chronic GVHD 
Day 100, end of taper, monthly during follow-up 
Follow-up 
Monthly during follow-up (until Day 365) 
Death 
Time of death 
Immunosuppressive Medications 
Days 14, 28, 42, 74, 100, Taper Period, and Follow-Up 
Period. 
Adverse Events 
Continuous 
 
11.2 
Expansion Phase 
 
Case Report Form 
Submission Schedule 
Consent form 
Prior to starting treatment 
On Study 
Medical and Surgical History 
Treatment History 
Baseline 
CBC 
Screening, Days -3, 0-14, 21, 28, 35, 42, 60, 74, 100, 128, 
156, 180, end of itacitinib taper, monthly during follow-up 
Chimerism 
Screening, Day 28, Day 35 (if applicable), Day 60, Day 100, 
128, 156, 180, end of taper period 
Correlative Studies  
Days , 3, 7, 14, 28, 100, 180, end of taper period 
Response Assessment  
Baseline and Day 28 (and Day 35 if applicable) 
FACT-BMT 
Human Activity Profile 1 of 2 
Human Activity Profile 2 of 2 
Baseline, Days 14, 28, 42, 74, 100, 128, 156, 180,  once 
during taper period, monthly during follow-up 
End of Treatment 
End of treatment 
Acute GVHD Assessment 
Days 14, 21, 28, 35, 42, 60, 100, 128, 156, 180, and end of 
itacitinib taper. 
Chronic GVHD 
Day 100, 128, 156, 180, end of taper, monthly during follow-
up 
Follow-up 
Monthly during follow-up (until Day 365) 
Death 
Time of death 
Immunosuppressive Medications 
Days 14, 28, 42, 74, 100, 128, 156, 180, Taper Period, and 


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Follow-Up Period. 
Adverse Events 
Continuous 
 
11.3 
Adverse Event Collection in the Case Report Forms 
 
All adverse events that occur beginning with start of treatment (minus exceptions defined 
in Section 12.0) must be captured in the Toxicity Form.  Baseline AEs should be captured 
on the Medical History Form. 
 
Participant death due to disease progression should be reported on the Toxicity Form as 
grade 5 disease progression.  If death is due to an AE (e.g. cardiac disorders: cardiac arrest), 
report as a grade 5 event under that AE.  Participant death must also be recorded on the 
Death Form. 
 
 
12.0 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outlined below.  Please refer to Appendix 9 for definitions and Appendix 10 for a grid of reporting 
timelines. 
 
Adverse events will be tracked from start of treatment with itacitinib through 30 days after the last 
dose of itacitinib.  Only selected AEs as described below will be collected on the toxicity trackin 
case report form and reviewed: 
• All grade 3, 4, or 5 AEs 
• Any AE that requires itacitinib treatment to be delayed, held, or discontinued.  
Hematological AEs will not be assessed from day -3 to day 35. 
• Any AE that requires modification of GVHD prophylaxis medications 
• Moderate and severe cases of VOD/SOS using the modified Seattle or Baltimore criteria. 
 
Baseline adverse events will be recorded on the medical history CRF. 
 
Refer to the data submission schedule in Section 11 for instructions on the collection of AEs in the 
EDC. 
 
12.1 
Sponsor-Investigator Reporting Requirements 
 
12.1.1 Reporting to the Human Research Protection Office (HRPO) at 
Washington University 
 
Reporting will be conducted in accordance with Washington University IRB 
Policies. 
 
Pre-approval of all protocol exceptions must be obtained prior to implementing the 
change. 
 


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12.1.2 Reporting to the Quality Assurance and Safety Monitoring Committee 
(QASMC) at Washington University 
 
The Washington University Sponsor-Investigator is required to notify the QASMC 
of any unanticipated problems involving risks to participants or others occurring at 
WU or any BJH or SLCH institution that has been reported to and acknowledged 
by HRPO.  (Unanticipated problems reported to HRPO and withdrawn during the 
review process need not be reported to QASMC.) 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via 
email to qasmc@wustl.edu.  Submission to QASMC must include the myIRB form 
and any supporting documentation sent with the form. 
 
12.1.3 Reporting to the FDA 
 
The conduct of the study will comply with all FDA safety reporting requirements.  
PLEASE NOTE THAT REPORTING REQUIREMENTS FOR THE FDA 
DIFFER FROM REPORTING REQUIREMENTS FOR HRPO/QASMC.  It 
is the responsibility of the Sponsor-Investigator to report to the FDA as follows: 
 
• Report any unexpected fatal or life-threatening suspected adverse reaction 
(refer to Appendix 9 for definitions) no later than 7 calendar days after 
initial receipt of the information.   
• Report a suspected adverse reaction that is both serious and unexpected 
(SUSAR, refer to Appendix 9) no later than 15 calendar days after it is 
determined that the information qualifies for reporting.  Report an adverse 
event (refer to Appendix 9) as a suspected adverse reaction only if there is 
evidence to suggest a causal relationship between the drug and the adverse 
event, such as: 
o A single occurrence of an event that is uncommon and known to be 
strongly associated with drug exposure 
o One or more occurrences of an event that is not commonly associated 
with drug exposure but is otherwise uncommon in the population 
exposed to the drug 
o An aggregate analysis of specific events observed in a clinical trial that 
indicates those events occur more frequently in the drug treatment 
group than in a concurrent or historical control group 
• Report any findings from epidemiological studies, pooled analysis of 
multiple studies, or clinical studies that suggest a significant risk in humans 
exposed to the drug no later than 15 calendar days after it is determined 
that the information qualifies for reporting. 
• Report any findings from animal or in vitro testing that suggest significant 
risk in humans exposed to the drug no later than 15 calendar days after it 
is determined that the information qualifies for reporting.  


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• Report any clinically important increase in the rate of a serious suspected 
adverse reaction of that listed in the protocol or IB within 15 calendar days 
after it is determined that the information qualifies for reporting. 
 
Submit each report as an IND safety report in a narrative format or on FDA Form 
3500A or in an electronic format that FDA can process, review, and archive.  Study 
teams must notify the Siteman Cancer Center Protocol Development team of each 
potentially reportable event within 1 business day after initial receipt of the 
information, and must bring the signed 1571 and FDA Form 3500A to the Siteman 
Cancer Center Protocol Development team no later than 1 business day prior to the 
due date for reporting to the FDA. 
 
Each notification to FDA must bear prominent identification of its contents (“IND 
Safety Report”) and must be transmitted to the review division in the Center for 
Drug Evaluation and Research (CDER) or in the Center for Biologics Evaluation 
and Research (CBER) that has responsibility for review of the IND.  Relevant 
follow-up information to an IND safety report must be submitted as soon as the 
information is available and must be identified as such (“Follow-up IND Safety 
Report”).   
 
12.1.4 Reporting to Incyte Corporation 
   
12.1.4.1 
SAE Reporting to Incyte 
 
The Principal Investigator (PI) must report all Serious Adverse Events 
(SAEs) to Incyte within 24 hours of learning of an event, regardless of the 
PI’s causality assessment. This notification should be provided on a 
completed Serious Adverse Event (SAE) form.  SAE reporting for each 
subject begins the day the informed consent is signed by the patient and 
within 30 days after subject has completed or discontinued from the study 
or has taken last dose of the study drug, or as described in the protocol. 
 
SAEs, occurring using Incyte study drug, are reported in accordance with 
the effective protocol.  SAEs occurring with any other commercial drug are 
reported to the manufacturer of that drug in accordance with regulations and 
protocol.  
 
Initial SAEs and/or subsequent follow-up reports should be reported via 
email to SafetyReporting@Incyte.com  or fax (+) 1-866-981-2057.  SAE 
reports should be for a single subject.  SAE forms should be sent with a 
cover sheet and any additional attachments.  
 
All adverse event information is reported to Incyte on the Principal 
Investigator’s/Institution’s Adverse Event Report Form, or a CIOMS-I or 
MedWatch Form FDA 3500A, or on an Adverse Event Report Form which 
may be provided by Incyte upon request. The Principal Investigator does 


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not provide medical records (e.g., discharge summary) to Incyte, unless 
specifically requested 
 
12.1.4.2 
Reporting a Pregnancy 
 
An “Initial Pregnancy Report” or equivalent must be completed in full and 
emailed to SafetyReporting@Incyte.com  or faxed to (+) 1-866-981-2057 
within 24 hours of 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  or faxed 
to (+) 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. 
 
12.2 
Exceptions to Expedited Reporting 
 
Events that do not require expedited reporting as described in Section 12.1 include: 
• planned hospitalizations 
• hospitalizations < 24 hours 
• respite care 
• events related to disease progression 
 
Events that do not require expedited reporting must still be captured in the EDC. 
 
 
13.0 
DATA AND SAFETY MONITORING   
 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, the 
Principal Investigator will provide a Data and Safety Monitoring (DSM) report to the Washington 
University Quality Assurance and Safety Monitoring Committee (QASMC) semi-annually 
beginning six months after accrual has opened (if at least five patients have been enrolled) or one 
year after accrual has opened (if fewer than five patients have been enrolled at the six-month mark). 
 
The Principal Investigator will review all patient data at least bi-monthly to evaluate for toxicity.  
There will be a review of study data after the lead in phase prior to continuation. A semi-annual 
report will be provided to the QASMC.  This report will include: 
• HRPO protocol number, protocol title, Principal Investigator name, data coordinator 
name, regulatory coordinator name, and statistician 
• Date of initial HRPO approval, date of most recent consent HRPO approval/revision, 
date of HRPO expiration, date of most recent QA audit, study status, and phase of study 
• History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol error(s), or 
breach of confidentiality including start/stop dates and reason 


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• Study-wide target accrual and study-wide actual accrual  
• Protocol activation date  
• Average rate of accrual observed in year 1, year 2, and subsequent years  
• Expected accrual end date 
• Objectives of protocol with supporting data and list the number of participants who 
have met each objective 
• Measures of efficacy  
• Early stopping rules with supporting data and list the number of participants who have 
met the early stopping rules 
• Summary of toxicities  
• Abstract submissions/publications 
• Summary of any recent literature that may affect the safety or ethics of the study  
 
The study principal investigator and Research Patient Coordinator will monitor for serious 
toxicities on an ongoing basis. Once the principal investigator or Research Patient Coordinator 
becomes aware of an adverse event, the AE will be reported to the HRPO and QASMC according 
to institutional guidelines. 
 
 
14.0 
STUDY EFFICACY AND DISCONTINUATION 
 
14.1 
Criteria to Measure Incidence and Severity of GVHD 
 
Acute GVHD will be assessed using MAGIC criteria (Appendix 2).  Chronic GVHD will 
be accessed using the NIH consensus criteria (Appendix 3).   
 
14.2 
Definitions for Safety and Efficacy Assessments  
 
14.2.1 Neutrophil Engraftment 
 
Time to neutrophil engraftment is measured by determining the first of 3 
consecutive measurements of neutrophil count ≥ 500/ul following conditioning 
regimen-induced nadir. 
 
14.2.2 Platelet Engraftment 
 
Time to platelet engraftment is measured by determining the first of 7 consecutive 
measurements of platelet count ≥ 20,000/ul without platelet transfusion support for 
7 days. 
 
14.2.3 Primary Graft Failure 
 
Failure of neutrophil engraftment by Day 35. 
 
14.2.4 Secondary Graft Failure  
 


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Primary engraftment followed by a drop in the neutrophil count to less than 500/ml 
for more than 3 consecutive days without any apparent cause such as drugs or 
opportunistic infection. 
 
14.2.5 Full Donor Chimerism 
 
Greater than or equal to 95% donor cells within the bone marrow. 
 
14.2.6 Acute GVHD 
 
Incidence and severity of acute GVHD will be assessed using MAGIC criteria 
(Appendix 2). Attempts should be made to confirm the diagnosis pathologically by 
biopsy of target organ(s). 
 
14.2.7 Steroid Refractory Acute GVHD 
 
Steroid refractory acute GVHD will be defined as no improvement in GVHD within 
7 days of starting systemic corticosteroids (2mg/kg/day prednisone equivalent) or 
progression of GVHD while on 2mg/kg steroids after 3 days of steroids. 
 
14.2.8 Chronic GVHD 
 
Incidence and severity of chronic GVHD will be assessed based on the NIH 
consensus criteria and global severity scoring system.  Attempts should be made to 
confirm the diagnosis pathologically by biopsy of target organ(s). 
 
14.2.9 Treatment-Related Mortality 
 
Death that results from a transplant procedure-related complication (e.g. infection, 
organ failure, hemorrhage, GVHD) rather than from relapse of the underlying 
disease or an unrelated cause. 
 
14.2.10 Adverse Events 
 
Adverse events will be assessed and graded according to NCI Common Toxicity 
Criteria version 5.0 as outlined in Section 12.1.1. 
 
14.2.11 Determination of Relapse 
 
A patient will be considered relapsed when there is a recurrence of the original 
malignant disease after transplantation. The time to relapse is the time from the date 
of transplant to date of the first observation of hematologic, radiographic, or 
cytogenetic changes, which result in characterization as relapse. 
 
14.2.12 Determination of Survival 
 


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Survival will be measured by assessing if the patient remains alive by visual 
observation, telephone call or notification of death medical record or death 
certificate. 
 
14.2.13 Evaluable for Toxicity 
 
All subjects will be evaluable for toxicity from the time of their first dose of 
itacitinib. 
 
14.2.14 Overall Survival 
 
Defined as the date of transplant to the date of death from any cause. 
 
14.2.15 Duration of Remission 
 
Defined as the interval from the date complete remission is documented to the date 
of recurrence. 
 
14.2.16 Disease-Free Survival 
 
Defined as the interval from the date of first documentation of a CR to date of 
relapse. 
 
14.3 
Response Review 
 
At the end of the study all responses will be reviewed by an expert independent of the 
study. 
 
 
15.0 
STATISTICAL CONSIDERATIONS   
 
15.1 
Study Design 
 
Overall design. This is an amendment to extend an ongoing promising pilot study to   
determine the safety and tolerability of itacitinib for the prevention of GVHD and cytokine 
release syndrome (CRS) with haplo-HCT. 
 
15.2 
Study Endpoints 
 
15.2.1 Pilot Study 
 
The primary safety endpoints will be rate of graft failure at Day 35 and occurrence 
of grade 3-4 acute GVHD by Day 100. 
 
The secondary endpoints will be rate of treatment related mortality by Day 180 and 
the incidence and severity of cytokine release syndrome. 


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15.2.2 Expansion Study 
 
The primary endpoint will be the cumulative incidence of acute GVHD grades 
III-IV at Day 100. 
 
The secondary endpoints will the cumulative incidence of acute GVHD grades II-
IV at Day 100, the incidence severity of cytokine release syndrome, and the 
cumulative incidence of treatment related mortality at day 180. 
 
15.3 
Sample Size Calculation 
 
15.3.1 Pilot Study 
 
A sample of 20 evaluable patients is a clinically feasible number to enroll and to 
provide estimates of the primary safety endpoints in this pilot study. Based on an 
extensive simulation study to determine the sample size for pilot and translational 
studies,  Piantadosi recommended that a sample size of 15-20 subjects will estimate 
the preliminary information with a reasonable precision.  Based on the experience 
of 200 patients undergoing haplo-HCT at our institution, our observed rate of 
engraftment failure in patients without DSAs is 9-10%, and our observed rate of 
grade III-IV acute GVHD is 13%.   
 
15.3.2 Expansion Study 
 
An expansion sample of 20 additional patients gives a total of N=40 patients treated 
with the study drug to evaluate the primary endpoint of acute GVHD grades III-IV 
at Day 100. In the ongoing pilot phase, no event of Grade 3/4 aGVHD or graft 
failure has been observed out of the first 19 evaluable patients. With the designed 
sample size (N=40), there will be high presion to estimate the treatment efficacy. 
Table below also shows the precision of estimation under various scenarious with 
20 and 40 patients respectively. If 2 Grade III-IV aGVHD are observed out of 40 
patients, for example, we will have 95% confidence that the “true” rate in the 
targeting population falls below 17%.  
 
# of grade III-
IV aGVHD) 
Rate of grade III-IV aGVHD 
(95% CI) with N=20 
Rate of grade III-IV aGVHD 
(95% CI) with N=40 
0 
 0% (0 – 16.8%) 
0% (0 -8.8%) 
1 
5% (0.1 -24.9%) 
2.5% (0.1 – 13.2%) 
2 
10% (1.2 -31.7%) 
5% (0.6-16.9%) 
3 
15% (3.2 – 37.9%) 
7.5% (1.6-20.4%) 
4 
20% (5.7 – 43.7%) 
10% (2.8-23.7%) 
5 
25% (8.7-49.1%) 
12.5% (4.2-26.8%) 
6 
30% (11.9-54.3%) 
15% (5.7-29.8%) 
 


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15.4 
Statement of Feasibility 
 
The leukemia and blood and marrow transplant division at Washington University is 
uniquely positioned to conduct this pilot study, as well as follow up efficacy trials, 
exploring JAK inhibition to prevent CRS and GVHD. We perform approximately 150 
allogeneic transplants annually of which 40-50 are haploidentical transplants.  We have a 
large clinical trial infrastructure and support staff performing over 500 clinical research 
studies.  We have dedicated transplant specific CRAs and data coordinators and a dedicated 
clinical research pharmacy and laboratory.  The DiPersio lab is experienced in conducting 
correlative studies and is well versed in the methods proposed for this study. 
 
After the safety lead in phase, we enrolled 18 patients to the pilot study in 11 months, which 
completed enrollment.  
 
15.5 
Statistical Analyses 
 
15.5.1 Descriptive Analysis 
 
15.5.1.1 
Patient Disposition 
 
The number of patients discontinued, the reasons for discontinuation, and 
the amount of therapy administered will be summarized by patient and by 
reason for discontinuation. 
 
15.5.1.2 
Protocol Deviations 
 
All significant deviations will be summarized by patient and by type of 
deviation. 
 
15.5.1.3 
Demographics and Baseline Characteristics 
 
Descriptive summary statistics will be provided for demographic and 
important baseline characteristics including gender, age, performance status, 
FAB/WHO AML subtype, and cytogenetic abnormalities.  For continuous 
variables, the number of patients, mean, standard deviation, median, 
minimum and maximum will be provided.  For categorical variables the 
number and percentage of patients in each category will be summarized. 
 
15.5.2 Primary Endpoint Analysis 
 
15.5.2.1 
Safety monitoring rule for Pilot Study 
 
A continuous bivariate Bayesian monitoring rule will be used to ensure that 
the rate of engraftment is sufficiently high and the rate of acute GVHD 
grades III-IV is acceptably low.   The rates of engraftment and acute GVHD 
grades III-IV will be monitored simultaneously after each patient50–52.  


Version 06/01/23 
 
Page 55 of 81 
Historical data on 200 patients at this institution indicates that 90% of 
patients are expected to have engraftment and 13% to experience acute 
GVHD grades III-IV. The minimum acceptable rate of engraftment is 80%, 
a decrease of 10%, and the maximum allowable rate of acute GVHD grades 
III-IV is 18%, an increase of 5%. The occurrence of engraftment and acute 
GVHD grades III-IV are considered to be independent. The probabilities of 
engraftment and acute GVHD grades III-IV for the historical data are 
modeled by beta distributions (beta (90, 10) and beta (13, 87), respectively).  
The prior probabilities of engraftment and toxicity for the experimental 
regimen are also modeled by beta distributions (beta (1.8, 0.2) and beta 
(0.26, 1.74), respectively). The posterior probability that the study treatment 
is more toxic that the standard treatment at this institution is .80. Patients 
experiencing either primary or secondary graft failure will be counted as 
engraftment failure towards stopping rules. Decision criteria are described 
in the following plot and table: 
 
 
 
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20
Continuous monitoring of engraftment and acute 
GVHD grades 3-4
Stop if # with engraftment falls ON OR BELOW this line
Stop if # with acute GVHD grade 3-4 falls ON OR ABOVE this line


Version 06/01/23 
 
Page 56 of 81 
# 
Patients 
Step if # with engraftment 
fall ON OR BELOW this 
number: 
Stop if # with acute GVHD 
grade 3-4 falls ON OR 
ABOVE this number: 
1 
Never stop 
Never stop 
2 
Never stop 
Never stop 
3 
2 
2 
4 
3 
2 
5 
4 
3 
6 
5 
3 
7 
5 
3 
8 
6 
3 
9 
7 
4 
10 
8 
4 
11 
9 
4 
12 
10 
4 
13 
11 
4 
14 
12 
5 
15 
13 
5 
16 
14 
5 
17 
15 
5 
18 
16 
6 
19 
17 
6 
20 
Always stop 
Always stop 
 
15.5.3 Final analysis of primary endpoint 
 
The cumulative incidence of grade 3 and 4 aGVHD at day 100 and its 95% 
confidence interval will be estimated using Fine-Gray’s sub-distribution model 
(treating death as competing risks).  
 
15.5.4 Secondary Endpoint Analysis 
 
Incidence of adverse events will be documented as proportions with 95% exact 
binomial confidence intervals patient, type and grade. A continuous toxicity 
monitoring rule will be used to assess treatment related mortality at day 180 
(tabulated below), assuming an historical rate of 10% and allowing a maximum of 
4 cases among 20 patients. The probability of correct early stopping if the TRM at 
day 180 rate reaches 5 in 20 (25%) is .6753. Fine-Gray models will be used to 
estimate the cumulative incidence of treatment-related mortality at d+30 (death and 
relapse as competing risks), relapse at 1 year (death as competing risk), and the 1 
year cumulative incidence of infection, acute GVHD grades 2-4, acute GVHD 
grades 3-4 and chronic GVHD at 1 year. The start time for chronic GVHD 
incidence will be day +80. Proportional hazards models will be used to estimate 1 
year rates of death of any cause (overall survival), relapse free survival and GVHD 
+ relapse free survival (GRFS). We acknowledge that the sample size of this pilot 
study will limit the precision of estimates from these models. 


Version 06/01/23 
 
Page 57 of 81 
 
# Patients 
Stop if # TRM at day 180 
EXCEEDS this number: 
1 
Never stop 
2 
1 
3 
1 
4 
1 
5 
2 
6 
2 
7 
2 
8 
2 
9 
3 
10 
3 
11 
3 
12 
3 
13 
3 
14 
3 
15 
4 
16 
4 
17 
4 
18 
4 
19 
4 
20 
Always stop 
 
15.5.5 Safety Analysis  
 
Subjects who receive at least one dose of itacitinib will be monitored for safety.  
AEs will be coded according to CTCAE v 5.0.  The results will be tabulated to 
examine their frequency, organ systems affected, and relationship to study 
treatment.  
 
The results of laboratory assessments will be evaluated similarly.  Interim safety 
data will be examined on an ongoing basis to ensure subject safety. In addition the 
Quality Assurance and Safety Monitoring Committee (QASMC) will review the 
DSM semi-annually. 
 
Applicable laboratory parameters will be graded according to NCI CTCAE v5.0.  
The incidence of maximum grade (number and percent of patients experiencing the 
maximum grade during the study) will be summarized for each laboratory 
parameter. Graphical display of selected hematological parameters will also be 
provided. 
 
Vital signs, physical examination findings, ECOG performance status scores, and 
weights will be presented in listing format. 


Version 06/01/23 
 
Page 58 of 81 
 
15.5.6 Stopping Rules  
 
See Section 15.4.2 above. 
 
 


Version 06/01/23 
 
Page 59 of 81 
 
16.0 
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APPENDIX 1: ECOG Performance Status Scale 
 
 
Grade 
 
 
Description 
0 
Normal activity.  Fully active, able to carry on all pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically strenuous 
activity, but ambulatory and able to carry out work of a light or 
sedentary nature (e.g., light housework, office work). 
2 
In bed <50% of the time.  Ambulatory and capable of all self-care, but 
unable to carry out any work activities.  Up and about more than 50% 
of waking hours. 
3 
 
In bed >50% of the time.  Capable of only limited self-care, confined 
to bed or chair more than 50% of waking hours. 
 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair. 
5 
 
Dead. 
 
 
 
 
 
 


Version 06/01/23 
 
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APPENDIX 2: Acute GVHD Assessment 
 
MAGIC CRITERIA FOR STAGING AND GRADING FOR ACTUE GVHD 
 
Stage 
Skin 
(Active Erythema 
Only) 
Liver 
(Bilirbuin) 
Upper GI 
Lower GI 
(Stool Output/Day) 
 
Overall Clinical Grade 
 
Grade 0: 
No stage 1-4 of any organ 
 
Grade I: 
Skin Stage 1-2 (without 
liver, upper GI, or lower 
GI) 
 
Grade II: 
Stage 3 rash and/or Stage 1 
liver and/or Stage 1 upper 
GI and/or Stage 1 lower GI 
 
Grade III: 
Stage 2-3 liver and/or Stage 
2-3 lower GI with Stage 0-3 
Skin and/or Stage 0-1 upper 
GI 
 
Grade IV: 
Stage 4 skin, liver, or lower 
GI with Stage 0-1 upper GI 
0 
No active 
(erythematous) 
GVHD rash 
< 2 mg/dL 
No or 
intermittent 
nausea, 
vomiting, or 
anorexia 
Adult: < 500 mL/day or < 
3 episodes day 
Child: < 10 mL/kg per 
day or < 4 episodes/day 
1 
Maculpapular rash 
< 25% BSA 
2-3 mg/dL 
Persistent 
nausea, 
vomiting, or 
anorexia 
Adult: 500-900 mL/day 
or 3-4 episodes day 
Child: 10-19.9 mL/kg per 
day or 4-6 episodes/day 
2 
Maculpapular rash 
25-50% BSA 
3.1-6 
mg/dL 
- 
Adult: 1000-1500 
mL/day or 5-7 episodes 
day 
Child: 20-30 mL/kg per 
day or 7-10 episodes/day 
3 
Maculpapular rash 
> 50% BSA 
6.1-15 
mg/dL 
- 
Adult: > 1500 mL/day or 
> 7 episodes day 
Child: > 30 mL/kg per 
day or > 10 episodes/day 
4 
Generalized 
erythroderma (> 
50% BSA) plus 
bullous formation 
and desquamation 
> 5% BSA 
> 15 
mg/dL 
- 
Severe abdominal pain 
with or without ileus or 
grossly bloody stool 
(regardless of stool 
volume) 
 
 
 
 
Acute GVHD Specifications 
Chronic GVHD Specifications 
• _____________%BSA 
• Stool Output: 
_____________mL/day OR 
episodes/day. 
• Grade: _____________ 
• ECOG: _____________ 
Does the subject have signs/symptoms of Chronic 
GVHD? ___________ 
• If yes, please circle overall grade and describe: 
Mild / Moderate / Severe 
• Describe:_____________________________ 
_____________________________________. 
 
 
Signature 
 
 
 
 
 
 
Date 
 
 


Version 06/01/23 
 
Page 65 of 81 
 
Date of Acute GVHD staging and grading 
 
 
Skin rash extent (% of BSA) 
 
 
Skin rash stage 
□ Stage 0 
□ Stage 1 
□ Stage 2 
□ Stage 3 
□ Stage 4 
Stool output (episodes per day) 
 
 
Stool output (estimated total volume in mL per day)  
 
Lower GI stage 
□ Stage 0 
□  Stage 1 
□  Stage 2 
□  Stage 3 
□  Stage 4 
Upper GI stage 
□  Stage 0 
□  Stage 1 
□  Stage 2 
□  Stage 3 
□  Stage 4 
Upper GI features due to GVHD 
□  Persistent nausea 
□  Persistent vomiting 
□  Persistent anorexia 
□  None 
Liver stage 
□  Stage 0 
□  Stage 1 
□  Stage 2 
□  Stage 3 
□  Stage 4 
MAGIC Criteria Overall Clinical Grade 
□  Grade 0 
□  Grade I 
□  Grade II 
□  Grade III 
□  Grade IV 
Did the subject experience a GVHD flare since the 
last visit? 
□  No 
□  Yes 
 
 


Version 06/01/23 
 
Page 66 of 81 
 
APPENDIX 3: Chronic GVHD Assessment 
 
 
Does the patient have a diagnostic feature of cGVHD per NCCN Guidelines Version 2.2020?  
 Yes       
 No    
 
If “No”, skip remainder of cGVHD assessment.  If “Yes”, proceed. 
 
Date of diagnosis of cGVHD  __________ 
 
 
 
0 
1 
2 
3 
Skin 
Score 
  No 
Symptoms 
  <18% BSA with 
disease signs but NO 
sclerotic features 
  19-50% BSA OR 
involvement with 
superficial sclerotic 
features “not 
hidebound” (able to 
pinch) 
 
 
  >50% BSA OR deep 
sclerotic features 
“hidebound” (unable to 
pinch) OR impaired 
mobility, ulceration or 
severe pruritus 
 
Mouth 
Score 
  No 
symptoms 
  Mild symptoms 
with disease signs 
but not limiting oral 
intake significantly 
  Moderate 
symptoms with signs 
with partial limitation 
of oral intake 
  Severe symptoms 
with disease signs on 
examination with major 
limitation of oral intake 
GI Tract 
Score 
(symptoms 
averaged 
over the last 
3 days) 
  No 
symptoms 
  Symptoms such 
as dysphagia, 
anorexia, nausea, 
vomiting, abdominal 
pain or diarrhea 
without significant 
weight loss (<5%) 
  Symptoms 
associated with mild to 
moderate weight loss  
(5-15%) 
  Symptoms associated 
with significant weight 
loss >15%, requires 
nutritional supplement 
for most calorie needs OR 
esophageal dilation 
Eye 
Score 
  No 
symptoms 
  Mild dry eye 
symptoms not 
affecting ADL 
(requiring eye drops  
≤3x per day) OR 
asymptomatic signs 
of kerato-
conjunctivitis sicca 
  Moderate dry eye 
symptoms partially 
affecting ADL 
(requiring eye drops 
>3x per day or 
punctual plugs) 
WITHOUT vision 
impairment 
  Severe dry eye 
symptoms significantly 
affecting ADL (special 
eyewear to relieve pain) 
OR unable to work 
because of ocular 
symptoms OR loss of 
vision caused by kerato-
conjunctivitis sicca 


Version 06/01/23 
 
Page 67 of 81 
Joint 
and 
Fascia 
Score 
  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 
  Contracture WITH 
significant decrease of 
ROM AND significant 
limitation of ADL (unable 
to tie shoes, button shirts, 
dress self etc.) 
Genital 
Tract 
Score 
(score even if 
no GYN exam, 
required for 
men too) 
 
 No GYN 
Exam 
  No 
symptoms 
  Symptomatic 
with mild distinct 
signs on exam AND 
no effect on coitus 
and minimal 
discomfort with GYN 
exam 
  Symptomatic with 
distinct signs on exam 
AND with mild 
dyspareunia or 
discomfort with GYN 
exam 
  Symptomatic WITH 
advanced signs (stricture, 
labia agglutination or 
severe ulceration) AND 
severe pain with coitus or 
inability to insert vaginal 
spectrum 
Lung 
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 O2) 
Liver 
Score 
 Normal 
LFTs 
  Elevated 
bilirubin, alkaline 
phosphatase, AST or 
ALT <2x ULN 
  Bilirubin > 3 mg/dl 
or bilirubin, AST or 
ALT 2-5x ULN 
  Bilirubin, AST or ALT 
> 5x ULN 
 
Liver score to be completed using most recent LFTs from within +/- 2 weeks of the assessment 
 
Date LFT sample obtained __________ 
 
 
PFT values from within one month of the assessment 
 
% FEV1   _______%    Date of FEV1 __________ 
 
 
 Not done    
 
% DLCOc   ______%    Date of DLCOc _________ 
 
 
 Not done 
 
 
Is an erythematous or maculopapular rash present?        
 Yes       
 No    
 
Does the patient have nausea, vomiting or diarrhea?       
 Yes       
 No    
 
 
Previous assessment of NIH severity grade  __________ 
 


Version 06/01/23 
 
Page 68 of 81 
Please rate the severity of this person’s chronic GVHD 
on this 
scale    
 None (1) 
 Mild (2) 
 Moderate  
(3) 
 Severe  (4) 
 
 
 
 
 
and on 
this 
scale  
 
 
(circle 
one) 
 
 cGVHD 
symptoms 
are not at 
all severe 
cGVHD  
symptoms 
are most 
severe  
possible 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
Date 
 
 
 


Version 06/01/23 
 
Page 69 of 81 
APPENDIX 4: FACT-BMT (Version 4) 
 
Below is a list of statements that other people with your illness have said are important. Please circle or 
mark one number per line to indicate your response as it applies to the past 7 days. 
 
 
PHYSICAL WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
GP1 
I have a lack of energy  
0 
1 
2 
3 
4 
GP2 
I have nausea  
0 
1 
2 
3 
4 
GP3 
Because of my physical condition, I have trouble 
meeting the needs of my family  
 
0 
 
1 
 
2 
 
3 
 
4 
GP4 
I have pain  
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment  
0 
1 
2 
3 
4 
GP6 
I feel ill  
0 
1 
2 
3 
4 
GP7 
I am forced to spend time in bed 
0 
1 
2 
3 
4 
 
 
SOCIAL/FAMILY WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
GS1 
I feel close to my friends 
0 
1 
2 
3 
4 
GS2 
I get emotional support from my family 
0 
1 
2 
3 
4 
GS3 
I get support from my friends 
0 
1 
2 
3 
4 
GS4 
My family has accepted my illness 
0 
1 
2 
3 
4 
GS5 
I am satisfied with family communication about my 
illness 
 
0 
 
1 
 
2 
 
3 
 
4 
GS6 
I feel close to my partner (or the person who is my main 
support) 
 
0 
 
1 
 
2 
 
3 
 
4 
Q1 
Regardless of your current level of sexual activity, please 
answer the following question. If you prefer not to answer it, 
please mark this box           and go to the next section. 
 
 
 
 
 
GS7 
I am satisfied with my sex life 
0 
1 
2 
3 
4 


Version 06/01/23 
 
Page 70 of 81 
Please circle or mark one number per line to indicate your response as it applies to the past 
7 days. 
 
 
EMOTIONAL WELL-BEING 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
GE1 
I feel sad 
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with my illness 
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my illness 
0 
1 
2 
3 
4 
GE4 
I feel nervous 
0 
1 
2 
3 
4 
GE5 
I worry about dying 
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get worse 
0 
1 
2 
3 
4 
 
 
 
FUNCTIONAL WELL-BEING 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GF1 
I am able to work (include work at home) 
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is fulfilling 
0 
1 
2 
3 
4 
GF3 
I am able to enjoy life 
0 
1 
2 
3 
4 
GF4 
I have accepted my illness 
0 
1 
2 
3 
4 
GF5 
I am sleeping well 
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for fun 
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right now 
0 
1 
2 
3 
4 
 
 
 


Version 06/01/23 
 
Page 71 of 81 
Please circle or mark one number per line to indicate your response as it applies to the past 
7 days. 
 
 
ADDITIONAL CONCERNS 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
BMT1 
I am concerned about keeping my job (include work at 
home)
 
0 
 
1 
 
2 
 
3 
 
4 
BMT2 
I feel distant from other people 
0 
1 
2 
3 
4 
BMT3 
I worry that the transplant will not work 
0 
1 
2 
3 
4 
BMT4 
The effects of treatment are worse than I had imagined 
0 
1 
2 
3 
4 
C6 
I have a good appetite 
0 
1 
2 
3 
4 
C7 
I like the appearance of my body 
0 
1 
2 
3 
4 
BMT5 
I am able to get around by myself 
0 
1 
2 
3 
4 
BMT6 
I get tired easily 
0 
1 
2 
3 
4 
BL4 
I am interested in sex 
0 
1 
2 
3 
4 
BMT7 
I have concerns about my ability to have children 
0 
1 
2 
3 
4 
BMT8 
I have confidence in my nurse(s) 
0 
1 
2 
3 
4 
BMT9 
I regret having the bone marrow transplant 
0 
1 
2 
3 
4 
BMT10 
I can remember things 
0 
1 
2 
3 
4 
Br1 
I am able to concentrate 
0 
1 
2 
3 
4 
BMT11 
I have frequent colds/infections 
0 
1 
2 
3 
4 
BMT12 
My eyesight is blurry 
0 
1 
2 
3 
4 
BMT13 
I am bothered by a change in the way food tastes 
0 
1 
2 
3 
4 
BMT14 
I have tremors 
0 
1 
2 
3 
4 
B1 
I have been short of breath 
0 
1 
2 
3 
4 
BMT15 
I am bothered by skin problems (e.g., rash, itching) 
0 
1 
2 
3 
4 
BMT16 
I have trouble with my bowels 
0 
1 
2 
3 
4 
BMT17 
My illness is a personal hardship for my close family 
members
 
0 
 
1 
 
2 
 
3 
 
4 
BMT18 
The cost of my treatment is a burden on me or my 
family
..........................................................................................
 
0 
 
1 
 
2 
 
3 
 
4 


Version 06/01/23 
 
Page 72 of 81 
APPENDIX 5: Human Activity Profile 
This is a list of common physical activities.  For each activity, check whether you currently engage in it, no 
longer engage in it, or have never engaged in it.  The best way to decide is to ask yourself whether you 
would engage in the activity today if you had the opportunity.  Please read the instructions and then 
complete the items as accurately as you can. 
 
Patient Initials:   
 
 
 
 
 
 
Study ID#:   
 
 
 
 
 
Still 
Doing 
Stopped 
Doing 
Never 
Did 
1. Getting in or out of chairs or bed (without assistance) 
 
 
 
2. Listening to the radio 
 
 
 
3. Reading books, magazines, or newspapers 
 
 
 
4. Writing (letters, notes) 
 
 
 
5. Working at a desk or table 
 
 
 
6. Standing (for more than 1 minute) 
 
 
 
7. Standing (for more than 5 minutes) 
 
 
 
8. Dressing or undressing (without assistance) 
 
 
 
9. Getting clothes from drawers or closets 
 
 
 
10. Getting in or out of a car (without assistance) 
 
 
 
11. Dining at a restaurant 
 
 
 
12. Playing cards/table games 
 
 
 
13. Taking a bath (no assistance needed) 
 
 
 
14. Putting on shoes, stockings, or socks (no rest or break needed) 
 
 
 
15. Attending a movie, play, church event, or sports activity 
 
 
 
16. Walking 30 yards (27 meters) 
 
 
 
17. Walking 30 yards (nonstop) 
 
 
 
18. Dressing/undressing (no rest or break needed) 
 
 
 
19. Using public transportation or driving a car (99 miles or less) 
 
 
 
20. Using public transportation or driving a car (100 miles or more) 
 
 
 
21. Cooking your own meals 
 
 
 
22. Washing or drying dishes 
 
 
 
23. Putting groceries on shelves 
 
 
 
24. Ironing or folding clothes 
 
 
 
25. Dusting/polishing furniture or polishing a car 
 
 
 
26. Showering 
 
 
 
27. Climbing 6 steps 
 
 
 
28. Climbing 6 steps (nonstop) 
 
 
 
29. Climbing 9 steps 
 
 
 
30. Climbing 12 steps 
 
 
 
31. Walking ½ block on level ground 
 
 
 
32. Walking ½ block on level ground (nonstop) 
 
 
 
33. Making a bed (not changing sheets) 
 
 
 
34. Cleaning windows 
 
 
 
35. Kneeling, squatting to do light work 
 
 
 
36. Carrying a light load of groceries 
 
 
 
37. Climbing 9 steps (nonstop) 
 
 
 
38. Climbing 12 steps (nonstop) 
 
 
 
39. Walking ½ block uphill 
 
 
 
40. Walking ½ block uphill (nonstop) 
 
 
 
41. Shopping (by yourself) 
 
 
 
42. Washing clothes (by yourself) 
 
 
 
43. Walking 1 block on level ground 
 
 
 
44. Walking 2 blocks on level ground 
 
 
 


Version 06/01/23 
 
Page 73 of 81 
 
Still 
Doing 
Stopped 
Doing 
Never 
Did 
45. Walking 1 block on level ground (nonstop) 
 
 
 
46. Walking 2 blocks on level ground (nonstop) 
 
 
 
47. Scrubbing (floors, walls, or cars) 
 
 
 
48. Making a bed (changing sheets) 
 
 
 
49. Sweeping 
 
 
 
50. Sweeping (5 minutes nonstop) 
 
 
 
51. Carrying a large suitcase or bowling (one game) 
 
 
 
52. Vacuuming carpets 
 
 
 
53. Vacuuming carpets (5 minutes nonstop) 
 
 
 
54. Painting (interior/exterior) 
 
 
 
55. Walking 6 blocks on level ground 
 
 
 
56. Walking 6 blocks on level ground (nonstop) 
 
 
 
57. Carrying out the garbage 
 
 
 
58. Carrying a heavy load of groceries 
 
 
 
59. Climbing 24 steps 
 
 
 
60. Climbing 36 steps 
 
 
 
61. Climbing 24 steps (nonstop) 
 
 
 
62. Climbing 36 steps (nonstop) 
 
 
 
63. Walking 1 mile 
 
 
 
64. Walking 1 mile (nonstop) 
 
 
 
65. Running 110 yards (100 meters) or playing softball/baseball 
 
 
 
66. Dancing (social) 
 
 
 
67. Doing calisthenics or aerobic dancing (5 minutes nonstop) 
 
 
 
68. Mowing the lawn (power mower but not a riding mower) 
 
 
 
69. Walking 2 miles 
 
 
 
70. Walking 2 miles (nonstop) 
 
 
 
71. Climbing 50 steps (2 ½ floors) 
 
 
 
72. Shoveling, digging, or spading 
 
 
 
73. Shoveling, digging, or spading (5 minutes nonstop) 
 
 
 
74. Climbing 50 steps (nonstop) 
 
 
 
75. Walking 3 miles or golfing 18 holes without a riding cart 
 
 
 
76. Walking 3 miles (nonstop) 
 
 
 
77. Swimming 25 yards 
 
 
 
78. Swimming 25 yards (nonstop) 
 
 
 
79. Bicycling 1 mile 
 
 
 
80. Bicycling 2 miles 
 
 
 
81. Bicycling 1 mile (nonstop) 
 
 
 
82. Bicycling 2 miles (nonstop) 
 
 
 
83. Running or jogging ¼ mile 
 
 
 
84. Running or jogging ½ mile 
 
 
 
85. Playing tennis or racquetball 
 
 
 
86. Playing basketball/soccer (game play) 
 
 
 
87. Running or jogging ¼ mile (nonstop) 
 
 
 
88. Running or jogging ½ mile (nonstop) 
 
 
 
89. Running or jogging 1 mile 
 
 
 
90. Running or jogging 2 miles 
 
 
 
91. Running or jogging 3 miles 
 
 
 
92. Running or jogging 1 mile in 12 minutes or less 
 
 
 
93. Running or jogging 2 miles in 20 minutes or less 
 
 
 
94. Running or jogging 3 miles in 30 minutes or less 
 
 
 
Fix, A.J., and D.M. Daughton, Human Activity Profile Professional Manual. Odessa, Fla: Pyschololgical 
Assessment Resources, Inc; 1988. 


Version 06/01/23 
 
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APPENDIX 6: Immunosuppressive Medication Questionnaire 
 
This form should be completed by the patients RN, NP, or MD 
 
Date of Assessment: _________________________              
 
Current Daily Tacrolimus Dose____________________________mg 
 
 
List any other medication administered for immunosupression within the past 30 days 
 
Drug__________________________ Daily Dose___________________________ 
 
Start Date______________________ Stop Date__________________________ 
 
 
Drug__________________________ Daily Dose___________________________ 
 
Start Date______________________ Stop Date__________________________ 
 
 
Drug__________________________ Daily Dose___________________________ 
 
Start Date______________________ Stop Date__________________________ 
 
 
Add additional lines below as needed 
 
 
 
 
 
Printed Name_____________________________ Signature_____________________________ 


Version 06/01/23 
 
Page 75 of 81 
APPENDIX 7: ASTCT CRS Grading System 
 
 
 
 
 
Patient name: ___________________           DOB:__________________ 
 
 
Date of Evaluation: ____________________________________________ 
 
 
CRS Grade:  
 0       
 1       
 2    
 3       
 4    
 5 (Death) 
 
 
 
 
 
 
 
 
 
Printed Name_____________________________ Signature_____________________________ 
 
 


Version 06/01/23 
 
Page 76 of 81 
APPENDIX 8: Medication Diary 
 
Today’s Date:    
 
     Study ID#:    
     Agent:  Itacitinib 
     Month:   
 
 
1. Complete one form for each month.  Take your dose of itacitinib once daily with or without food.  Take it with a 
glass of water and drink the glass of water in as little time as possible.  Swallow the pills whole and do not chew 
the capsules. 
2. Record the date, the number of pills taken, and when you took them. 
3. If you forgot to take your itacitinib dose and it’s been more than 6 hours since the regular dosing time, then do not 
take that dose.  Restart taking it with the next scheduled dose. 
4. If you have any questions or notice any side effects, please record them in the comments section.  Record the 
time if you should vomit. 
5. Please return the forms to your physician or study coordinator when you go to your next appointment.  Please 
bring your unused study pills and/or empty bottles with you to each clinic visit so that a pill count can be done. 
Day 
Date 
What time was dose taken? 
# of pills taken 
Comments 
1 
 
 
 
 
2 
 
 
 
 
3 
 
 
 
 
4 
 
 
 
 
5 
 
 
 
 
6 
 
 
 
 
7 
 
 
 
 
8 
 
 
 
 
9 
 
 
 
 
10 
 
 
 
 
11 
 
 
 
 
12 
 
 
 
 
13 
 
 
 
 
14 
 
 
 
 
15 
 
 
 
 
16 
 
 
 
 
17 
 
 
 
 
18 
 
 
 
 
19 
 
 
 
 
20 
 
 
 
 
21 
 
 
 
 
22 
 
 
 
 
23 
 
 
 
 
24 
 
 
 
 
25 
 
 
 
 
26 
 
 
 
 
27 
 
 
 
 
28 
 
 
 
 
29 
 
 
 
 
30 
 
 
 
 
31 
 
 
 
 
 


Version 06/01/23 
 
Page 77 of 81 
APPENDIX 9: Definitions for Adverse Event Reporting 
 
A. Adverse Events (AEs) 
 
As defined in 21 CFR 312.32: 
 
Definition: any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug-related. 
 
Grading: the descriptions and grading scales found in the revised NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.  A 
copy of the CTCAE version 5.0 can be downloaded from the CTEP website. 
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the terms 
listed that should be used are those provided by the Department of Health and Human Services’ 
Office for Human Research Protections (OHRP).  A copy of this guidance can be found on 
OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
B. Suspected Adverse Reaction (SAR) 
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse event for which there is a reasonable possibility that the drug caused 
the adverse event.  “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event.  “Suspected adverse reaction” implies a 
lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug. 
 
C. Life-Threatening Adverse Event / Life Threatening Suspected Adverse Reaction  
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse drug event or suspected adverse reaction is considered “life-
threatening” if, in the view of the investigator, its occurrence places the patient at immediate 
risk of death. It does not include an adverse event or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death. 
 
D.  Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction 
 
As defined in 21 CFR 312.32: 
 
Definition:  an adverse event or suspected adverse reaction is considered “serious” if, in the 
view of the investigator, it results in any of the following outcomes: 
o Death 
o A life-threatening adverse event 


Version 06/01/23 
 
Page 78 of 81 
o Inpatient hospitalization or prolongation of existing hospitalization 
o A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
o A congenital anomaly/birth defect 
o Any other important medical event that does not fit the criteria above but, based upon 
appropriate medical judgment, may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed above 
 
E. Protocol Exceptions 
 
Definition: A planned change in the conduct of the research for one participant. 
 
F. Deviation 
 
Definition: Any alteration or modification to the IRB-approved research without prospective 
IRB approval.  The term “research” encompasses all IRB-approved materials and documents 
including the detailed protocol, IRB application, consent form, recruitment materials, 
questionnaires/data collection forms, and any other information relating to the research study. 
 
A minor or administrative deviation is one that does not have the potential to negatively impact 
the rights, safety, or welfare of participants or others or the scientific validity of the study. 
 
A major deviation is one that does have the potential to negatively impact the rights, safety, 
or welfare of participants or others or the scientific validity of the study. 
 
 


Version 06/01/23 
 
Page 79 of 81 
APPENDIX 10: Reporting Timelines 
 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Incyte 
Serious AND 
unexpected suspected 
adverse reaction 
 
 
Report no later than 15 calendar 
days after it is determined that 
the information qualifies for 
reporting 
 
Unexpected fatal or 
life-threatening 
suspected adverse 
reaction 
 
 
Report no later than 7 calendar 
days after initial receipt of the 
information 
 
Unanticipated 
problem involving risk 
to participants or 
others 
Report within 10 working days.  If 
the event results in the death of a 
participant enrolled at 
WU/BJH/SLCH, report within 1 
working day. 
Report via email after IRB 
acknowledgment 
 
 
Serious adverse event 
 
 
 
Report within 24 hours of learning 
of the event. 
Pregnancy 
 
 
 
Report within 24 hours of 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. 
Major deviation 
Report within 10 working days.  If 
the event results in the death of a 
participant enrolled at 
WU/BJH/SLCH, report within 1 
working day. 
 
 
 
A series of minor 
deviations that are 
being reported as a 
continuing 
noncompliance 
Report within 10 working days.   
 
 
 
Protocol exception 
Approval must be obtained prior to 
implementing the change 
 
 
 


Version 06/01/23 
 
Page 80 of 81 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Incyte 
Clinically important 
increase in the rate of 
a serious suspected 
adverse reaction of 
that list in the protocol 
or IB 
 
 
Report no later than 15 calendar 
days after it is determined that 
the information qualifies for 
reporting 
 
Complaints 
If the complaint reveals an 
unanticipated problem involving 
risks to participants or others OR 
noncompliance, report within 10 
working days.  If the event results 
in the death of a participant enrolled 
at WU/BJH/SLCH, report within 1 
working day.  Otherwise, report at 
the time of continuing review. 
 
 
 
Breach of 
confidentiality 
Within 10 working days. 
 
 
 
Incarceration 
If withdrawing the participant poses 
a safety issue, report within 10 
working days.   
 
If withdrawing the participant does 
not represent a safety issue and the 
patient will be withdrawn, report at 
continuing review. 
 
 
 
 
Routine Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Incyte 
Adverse event or SAE 
that does not require 
expedited reporting 
If they do not meet the definition of an 
unanticipated problem involving risks to 
participants or others, report summary 
information at the time of continuing review 
Adverse events will be 
reported in the toxicity 
table in the DSM report 
which is typically due 
every 6 months. 
The most current 
toxicity table from the 
DSM report is provided 
to the FDA with the 
IND’s annual report. 
 
Minor deviation 
Report summary information at the time of 
 
 
 


Version 06/01/23 
 
Page 81 of 81 
Routine Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Incyte 
continuing review. 
Complaints 
If the complaint reveals an unanticipated problem 
involving risks to participants or others OR 
noncompliance, report within 10 working days.  If 
the event results in the death of a participant 
enrolled at WU/BJH/SLCH, report within 1 
working day.  Otherwise, report at the time of 
continuing review. 
 
 
 
Incarceration 
If withdrawing the participant poses a safety 
issue, report within 10 working days.   
 
If withdrawing the participant does not represent a 
safety issue and the patient will be withdrawn, 
report at continuing review. 
 
 
 
 
 

ICF_002.pdf: 
 
FOR IRB USE ONLY 
IRB ID #: 201903114 
APPROVAL DATE: 08/13/24 
RELEASED DATE: 08/14/24 
EXPIRATION DATE: 08/12/25 
 
INFORMED CONSENT DOCUMENT – EXPANSION PHASE 
 
Project Title: 
A Single-Arm, Open-Label, Pilot Study and Expansion Study of JAK Inhibitor 
Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome after 
T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation 
 
Principal Investigator: 
Ramzi Abboud, M.D. 
 
Research Team Contact: 
Ramzi Abboud, M.D. – (314) 454-8304 
 
This consent form describes the research study and helps you decide if you want to participate.  It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant. By signing this 
form you are agreeing to participate in this study. 
• You should read and understand the information in this document including the procedures, 
risks and potential benefits.  
• If you have questions about anything in this form, you should ask the research team for more 
information before you agree to participate.   
• You may also wish to talk to your family or friends about your participation in this study. 
• Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
 
KEY INFORMATION    
The first section of this document contains some key points that the research team thought you would 
find important. The research study is described in more detail after this section. 
 
This is a research study conducted by Dr. Ramzi Abboud having to do with receiving a stem cell 
transplant from a haploidentical donor.  A stem cell is a type of cell found in the blood or bone marrow 
which helps form more blood cells.  The purpose of a stem cell transplant is to use the stem cells from a 
healthy donor to replace the diseased bone marrow in the recipient. You are invited to be in this study 
because you have been diagnosed with a hematologic (bone marrow and blood cells) malignancy and 
are planning to receive a stem cell transplant from a haploidentical donor. You should carefully consider 
the information in this consent document and discuss it with the research team. You should understand 
why you might want to participate, or why you might not want to participate. It is your choice whether 
to participate or not. Before you decide whether to be in this study, you may wish to consider other 
options that are available to you.  Instead of being in this study, you could get treatment or care for your 
cancer without being in a study, take part in another research study, or get no treatment.  
 
If you agree and sign this consent, you will be volunteering to participate in the research study. The 
research team must give you a copy of this signed consent document. 
 
1. What is the research study about?  
The purpose of this research study is to look at the effects (good and/or bad) of giving a drug called 
itacitinib when you receive your transplant in an effort to prevent or lessen the effect of GVHD and 
CRS while still effectively treating your disease.  
 


 
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2. Why should I consider participating? 
To prevent or lessen the effect of GVHD and CRS while still effectively treating your disease.  
 
3. What will I be asked to do?  
If you are eligible to participate and agree to continue in the study, you will begin taking itacitinib on 
Day -3, which is 3 days before your scheduled day of transplant (Day 0).  Itacitinib is an oral 
medication that you will need to take approximately the same time every day, with or without food.  
You will be asked to complete a medication diary which you will need to bring with you to each of 
your clinic visits. You will continue to take itacitinib through Day 180, followed by a 30 to 60 day 
taper period where you will take a lower dose of itacitinib.  This study includes some procedures you 
might have for your care if you weren’t in this study, which is described in further detail later in the 
consent document. Follow up will take place until one year following transplant.  You will have 
monthly visits from Day 241 until you reach that one year post-transplant time point.   
 
If you agree to take part in this study, your involvement will last for approximately one year (180-
240 days of treatment with itacitinib plus follow-up to one year post-transplant). 
 
You may choose to stop participating and withdraw from the study at any time. If you withdraw 
from the study, the research team may continue to use the information already collected about you.   
 
4. What are the risks?  
There are some risks to you if you agree to volunteer for this study. The most serious/most common 
risks are anemia (low red blood cells), pyrexia (fever), headache, platelet count decreased, and 
neutropenia. The risks to you are described in more detail later in this consent document.  
 
5. What are the benefits to me? To others?  
There may be no direct benefit to you. However, we hope that, in the future, other people might 
benefit from this study because it will help researchers learn more about how to prevent GVHD.   
 
6. Is there any financial cost to me?  
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition.  Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are 
normally required by your health plan/insurance. Incyte is providing the itacitinib at no cost to you. 
   
7. Will my information be confidential?  
Yes, your identity will be kept confidential. Your information will be available only to those who are 
working on this study.  
 
8. Who is the sponsor? 
The study is sponsored by Incyte, The American Society of Hematology, and the National Institutes 
of Health.  
 
 
The rest of this document provides more details about the study.  
 


 
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WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We invite you to participate in this research study because you have been 
diagnosed with a hematologic (bone marrow and blood cells) malignancy and are planning to receive a 
stem cell transplant from a haploidentical donor.  A stem cell is a type of cell found in the blood or bone 
marrow which helps form more blood cells.  The purpose of a stem cell transplant is to use the stem 
cells from a healthy donor to replace the diseased bone marrow in the recipient.  One of the side effects 
of a stem cell transplant is the development of graft versus host disease (GVHD).  GVHD occurs when 
some of the cells from the donor attack the recipient’s tissues, resulting in mild, moderate, or even life-
threatening side effects to the recipient’s skin, stomach, intestine, and liver.  Another side effect is 
cytokine release syndrome (CRS), which can cause fever, nausea, headache, rash, rapid heartbeat, low 
blood pressure, and trouble breathing. 
 
A haploidentical stem cell transplant is a type of transplant that occurs when a person who needs a 
transplant can’t find a donor who exactly  matches their tissue type (either among family members or 
through a matched unrelated donor).  When no matched donor is available, half-matched related 
(haploidentical) donors may be used. A haploidentical donor is a first degree relative such as a sibling, 
child, or parent.   
 
Itacitinib is considered investigational, which means that it has not been approved by the U.S. Food and 
Drug Administration.   
 
WHAT WILL HAPPEN DURING THIS STUDY? 
All procedures will be given in the inpatient or outpatient setting at Siteman Cancer Center unless you 
have made other arrangements with the study team. We feel it is important to remind you that any 
procedures regardless of whether they are tests you would have if you did not take part in the research or 
are research-related will require you to remain at the Siteman Cancer Center up to several hours to 
complete the necessary testing. There may also be a wide variability in the length of clinic visits due to 
the unique characteristics of your medical history and health condition as well as due to clinic factors 
such as physician availability, staffing shortages, and weather delays. This will also vary depending 
upon your needs at the visit as determined by your physician. It is important that you are able to be 
available to complete the procedures at each visit to ensure that your safety and treatment needs are met. 
 
Pre-Study Evaluations: 
Prior to treatment, an overall assessment of your health will need to be taken to see if you are eligible to 
continue to participate in the study. You will have the tests and procedures listed below.  
• Physical examination, including review of your medical history, height, weight, and performance 
status 
• Routine blood draw to check your blood counts and organ function (about 2 teaspoons of blood 
will be drawn from a vein in your arm) 
• Pregnancy test (if you are a woman of childbearing potential) 
• Echocardiogram or MUGA (multiple gated acquisition) scan to check how your heart is 
functioning 
• Blood draw to check your blood type and human leukocyte antigen (HLA) typing (a protein 
found on most cells in your body) (about 1 teaspoon of blood will be drawn) 


 
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• Blood draw for a virology screening to make sure you don’t test positive for hepatitis and HIV 
(about 1 tablespoon of blood will be drawn) 
• Blood draw for chimerism testing, which allows researchers to compare your blood cells before 
you receive the transplant to your blood cells after the transplant (about 2 teaspoons of blood will 
be drawn) 
• Bone marrow aspirate and biopsy to check the status of your disease; this is a procedure during 
which a few teaspoons of your bone marrow and a little of the tissue will be removed using a 
hollow needle 
• Two questionnaires to assess your quality of life (which will take approximately 15 minutes to 
complete) 
 
It is possible that after your medical history, tests, and procedures are reviewed, you will not be able to 
continue in this study. If this occurs, your study doctor will go over the reasons with you. 
 
Procedures throughout the study: 
If you are eligible to participate and agree to continue in the study, you will begin taking itacitinib on 
Day -3, which is 3 days before your scheduled day of transplant (Day 0).  If you are unable to receive 
your transplant for any reason, you will stop taking itacitinib and will come off study.  Itacitinib is an 
oral medication.  You will need to take it at approximately the same time every day, with or without 
food.  You will be asked to complete a medication diary which you will need to bring with you to each 
of your clinic visits.  You will continue to take itacitinib through Day 180, followed by a 30- to 60-day 
taper period where you will take a lower dose of itacitinib. 
If you are one of the first 3 patients enrolled in this study, the person who is donating cells for your 
transplant will also need to consent to this study.  We will be asking them if we can collect another batch 
of cells from them in case the itacitinib prevents the transplant from working properly.  If that happens, 
you will stop taking itacitinib and will come off study.  
 
While you are taking itacitinib, you will have the following tests and procedures: 
• Physical exam, review of medications, and evaluation of any side effects you may be 
experiencing  at the following time points: 
o daily from Day -3 through Day 14 
o weekly from Day 21 through Day 42 
o Day 60 
o Day 74 
o every 4 weeks from Day 100 until Day 365 
• Evaluation to see whether you are experiencing CRS at the following time points: 
o Day -3 
o Daily from Day 0 through Day 14 
o Day 21 
o Day 28 
• GVHD assessment beginning on Day 14 and then at all of the same time points as the physical 
exam 
• Routine blood draw to check your blood counts and organ function at the following time points: 
o daily from Day -3 through Day 14 
o weekly from Day 21 through Day 42 


 
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o Day 60 
o Day 74 
o Every 4 weeks from day 100 through Day 180 
o during the taper period as needed 
• Monthly follow up visits till day 365. Blood draw for chimerism testing at the following time 
points: 
o Day 28 
o Day 35 if your transplant hasn’t been successful 
o Day 60 
o Day 100 
o Day 180 
o Day 365 
• Questionnaires to assess your quality of life at the following time points: 
o Day 14 
o Day 28 
o Day 42 
o Day 60 
o Day 74 
o Day 100 
o Every 4 weeks from Day 128 to 180 
o monthly from Day 181 to 365 
 
• Bone marrow biopsy at the following time points: 
o Day 28 
o Day 35 if your transplant hasn’t been successful 
o Day 100 
o Day 180 
• Research blood tests on the following days: 
o Before the start of conditioning treatment for your transplant (approximately 7 tablespoons) 
o Day 3 (approximately 7 tablespoons) 
o Day 7 (approximately 2 tablespoons) 
o Day 14 (approximately 2 tablespoons) 
o Day 28 (approximately 6 tablespoons) 
o Day 60 (approximately 6 tablespoons) 
o Day 100 (approximately 4 tablespoons) 
o Day 180 (approximately 6 tablespoons) 
o Taper Period Days 180-240 (approximately 6 tablespoons) 
o Post Treatment (Between 14 and 35 days after the last dose of study drug) (approximately 6 
tablespoons) 
o If you are diagnosed with acute GVHD (approximately 2 tablespoons)  
 
These research tests will include genetic research, including whole exome sequencing (which 
determines the order of DNA building blocks in your individual genetic code). 
 
Follow-Up: 


 
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Follow-up will take place until one year following transplant.  You will have monthly visits from Day 
241 until you reach that one year post-transplant time point.  Each month, the following tests and 
procedures will take place: 
• Physical exam, review of medications, and evaluation of any side effects you may be 
experiencing 
• GVHD assessment 
• Questionnaires to assess your quality of life 
• Blood draw for chimerism (last follow-up visit only) 
 
Will you save my samples or research data to use in future research studies?  
As part of this study, we are obtaining bone marrow, blood, and data from you. We would like to use 
this bone marrow, blood, and data for studies going on right now as well as studies that are conducted in 
the future.  These studies may provide additional information that will be helpful in understanding blood 
cancers, or other diseases or conditions, including research to develop investigational tests, treatments, 
drugs or devices that are not yet approved by the U.S. Food and Drug Administration.  It is unlikely that 
what we learn from these studies will have a direct benefit to you.  There are no plans to provide 
financial compensation to you should this occur.  By allowing us to use your bone marrow, blood, and 
data you give up any property rights you may have in the bone marrow, blood, and data. 
 
We might remove identifiers from your private information and your bone marrow, blood, and data and 
then use the information and your bone marrow, blood, and data for future research studies or share 
them with other researchers for their future research. If this occurs we will not ask you for additional 
consent for these uses of your information or bone marrow, blood, and data.  
 
These studies may include genetic research. Genetic research can look at DNA to look for mutation 
(changes) that may increase the risk of disease or affect the way a person responds to treatment. This 
could include the database of Genotypes and Phenotypes (dbGaP), which is a repository that shares 
genomic data. The data within dbGaP remains anonymous, but de-identification of data cannot eliminate 
a risk of disclosure, which could affect you and even your family members. 
 
We will share your bone marrow, blood, and data with other researchers. They may be doing research in 
areas similar to this research or in other unrelated areas.  These researchers may be at Washington 
University, at other research centers and institutions, or industry sponsors of research.  We may also 
share your research data with large data repositories (a repository is a database of information) for broad 
sharing with the research community.  If your individual research data is placed in one of these 
repositories only qualified researchers, who have received prior approval from individuals that monitor 
the use of the data, will be able to look at your information.   
 
If you change your mind and do not want us to store and use your bone marrow, blood, and data for 
future research you should contact the research team member identified at the top of this document.  The 
bone marrow, blood, and data will no longer be used for research purposes. However, if some research 
with your bone marrow, blood, and data has already been completed, the information from that research 
may still be used. Also, if the bone marrow, blood, and data has been shared with other researchers it 
might not be possible to withdraw the bone marrow, blood, and data to the extent it has been shared. 
 
 


 
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Please place your initials in the blank next to Yes or No for each of the questions below: 
 
My bone marrow, blood, and data may be stored and used for future research as described above. 
 
_____ Yes 
_____ No 
Initials  
Initials 
 
My bone marrow, blood, and data may be shared with other researchers and used by these 
researchers for the future research as described above. 
 
_____ Yes  
_____ No 
Initials  
Initials 
 
Unless you agree to future use as described above, your private information your bone marrow, blood, 
and data collected as part of this study will not be used or distributed for future research studies, even if 
identifiers are removed. 
 
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 40 people will take part in this study conducted by investigators at Washington 
University. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study. 
 
Some risks described in this consent document, if severe, may cause death.  
 
Risks of Itacitinib 
Very Common (greater than or equal to 20%) 
• Anemia (low red blood cells) which could make you feel tired or dizzy 
• Pyrexia (fever) 
• Headache  
• Platelet count decreased 
• Neutropenia a condition in which you have a low number of white blood cells called neutrophils 
in your blood. This causes your immune system to be weakened, making it harder for your body 
to fight infection. 
 
Common (greater than or equal to 10%) 
• Hypophosphatemia (low phosphate) 
• Decreased appetite 
• Hypokalemia (low potassium) 
• Fatigue 
• Nausea 
• Pneumonia  
• Pneumonia pseudomonal  


 
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• Sepsis 
 
Rare, and severe 
• Graft failure can occur after haploidentical transplant (low blood counts after transplant requiring 
transfusions, antibiotics and other support). It is unknown if itacitinib will increase this 
incidence. Graft failure can result in death. 
 
Risks of Stem Cell Transplant 
The side effects of stem cell transplant may include GVHD, as well as the development of low blood 
counts. If you develop GVHD, you will be treated with steroids and other standard of care treatments for 
GVHD if necessary. If you develop low blood counts, you will be supported with blood transfusions, 
antibiotics, and G-CSF (a growth factor for white blood cells) as necessary.  
 
Specific effects of GVHD: 
• Bone marrow---low white blood cell, red blood cells and/or platelets---this may lead to 
requirements for transfusions or antibiotics 
• Gastrointestinal toxicity---can result in inflammation of intestines causing malabsorption or 
diarrhea 
• Liver toxicity---can lead to liver dysfunction or failure—can result in fluid accumulation or 
jaundice, which can lead to yellow skin and itching 
• Skin toxicity—can cause rash, thickened skin with decreased mobility, or skin sloughing 
 
Altered immune function is common after stem cell transplantation. You therefore have a significant 
risk of getting a variety of infections, including bacterial or fungal infections. Antibiotic or antifungal 
therapy will be given as medically indicated.  
 
Another side effect is cytokine release syndrome (CRS), which can cause fever, nausea, headache, rash, 
rapid heartbeat, low blood pressure, and trouble breathing. 
Rarely (5-10%) the stem cells transplanted fail to fully engraft the recipient. Patients who are not 
complete or are mixed chimeras (not all blood and bone marrow cells are replaced with donor cells) are 
at risk of bone marrow failure (the bone marrow is unable to produce enough blood cells) after the 
infusion of stem cells. The bone marrow failure may be lethal if the bone marrow does not recover 
afterwards. If you develop bone marrow failure, you will be supported with blood transfusions, 
antibiotics and growth factors until additional stem cells can be infused from the original donor. 
 
Risks of Blood Draw 
The blood draw may cause bleeding, bruising, or pain. Some people become dizzy or feel faint. There is 
also a rare risk of infection. 
 
Testing for Reportable Diseases  
If you decide to participate in this study, we will test you for HIV and hepatitis B and C. The results of 
these tests could indicate that you have one of these conditions. If that happens, we will refer you to a 
doctor who specializes in treating your condition. We will make every effort to keep your personal 
information confidential. However, we are required by law to report certain positive tests to the state of 
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Control.  You may be contacted by these agencies for more information.  Becoming aware of a new 
diagnosis could have serious health, personal and/or social consequences.  For more information about 
the risks of this testing, please talk to your study doctor. 
 
Risks of Bone Marrow Aspiration and Biopsy  
It is likely that you will experience discomfort or pain, redness, swelling, and bruising at the site of the 
needle insertion. It is less likely that you will experience bleeding from the site of the needle insertion. 
There is a rare chance (approximately less than 1/100) of developing a significant infection or bleeding 
from this procedure. An allergic reaction to the anesthetic may occur. A scar may form at the site of 
needle entry. 
 
Risks of Echocardiogram 
An echocardiogram is a test that uses sound waves to create a moving picture of the heart. An 
instrument that transmits high-frequency sound waves called a transducer is placed on your ribs near the 
breast bone and directed toward the heart. You should feel no pain with this test. You may experience 
discomfort from lying quietly for a long period of time. 
 
Risks of MUGA Scan 
The MUGA (Multiple Gated Acquisition) scan is used to assess the function of the heart. The MUGA 
scan produces a moving image of the beating heart, and from this image several important features can 
be learned about the health of your heart. A small amount of low-level radioactive substance (tracer) is 
injected into your vein and temporarily “labels” your red blood cells. Then the heart is scanned by a 
camera which can “see” the marked blood and produce the moving image. The final product is a movie 
of the heart beating. Allergic reactions to the tracer are rare. Most of the tracer will be eliminated from 
your body within a day. You may have some pain or swelling where the tracer is injected into your vein. 
 
Risks of Questionnaires  
Some of the questions may make you feel uncomfortable. You have the right to refuse to answer any 
question for any reason. 
 
Risks for Women Capable of Becoming Pregnant 
If you are a woman capable of becoming pregnant, we will ask you to have a pregnancy test before 
beginning this study.  You must use effective birth control methods and try not to become pregnant 
while participating in this study.  If you become pregnant, there may be unknown risks to your unborn 
child, or risks to your unborn child that we did not anticipate.  There may be long-term effects of the 
treatment being studied that could increase the risk of harm to an unborn child.  You must tell the doctor 
if your birth control method fails while you are on the study. If you believe or know you have become 
pregnant while participating in this research study, please contact the research team member identified at 
the top of this document as soon as possible.  Please discuss with the research team how long you need 
to wait before becoming pregnant after completing the treatment or procedures on this study. 
 
Risks for Sexually Active Males 
If you are a sexually active male it is important that your partner not become pregnant during your 
participation in this study.  There may be unknown risks to the unborn child or risks we did not 
anticipate.  You and your partner must agree to use birth control if you want to take part in this study.  If 
you believe or know that your partner has become pregnant during your participation in this study, 


 
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please contact the research team member identified at the top of this document as soon as possible 
 
Risks of Genetic Research 
There is a federal law called the Genetic Information Nondiscrimination Act (GINA). In general, this 
law makes it illegal for health insurance companies, group health plans and employers with greater than 
15 employees to discriminate against you based on your genetic information. However, it does not 
protect you against discrimination by companies that sell life insurance, disability insurance or long 
term-care insurance.  
 
Risk of Breach of Confidentiality 
One risk of participating in this study is that confidential information about you may be accidentally 
disclosed.  We will use our best efforts to keep the information about you secure.  Please see the section 
in this consent form titled “How will you keep my information confidential?” for more information. 
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you.  Instead of being in this study, you could: 
• get treatment or care for your cancer without being in a study 
• take part in another research study 
• get no treatment 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition.  Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are normally 
required by your health plan/insurance.  Not all insurance plans cover the costs associated with being in 
a study. Even if they do, you may be responsible for more out-of-pocket expenses, such as co-pays and 
deductibles, when there are more tests and procedures or more expensive tests and procedures involved 
in the study than if you were to receive routine clinical care outside the study.   
 
If you wish to know whether there are more tests and procedures or more expensive tests and procedures 
in the study, you should ask your study doctor.   
If you wish to know whether your insurance will pay, you should contact them directly, or speak with 
the study team about obtaining a financial pre-certification prior to enrolling in the study. 
 
Incyte is providing the itacitinib at no cost to you. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will not be paid for being in this research study.   
 
WHO IS FUNDING THIS STUDY? 
Incyte, the American Society of Hematology, and the National Institutes of Health (NIH) are funding 
this research study.  This means that Washington University is receiving payments from Incyte,  the 
American Society of Hematology, and the NIH to support the activities that are required to conduct the 
study.  No one on the research team will receive a direct payment or increase in salary from Incyte, the 
American Society of Hematology, or the NIH for conducting this study. 


 
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WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research. If you feel you are injured because of the study, please contact the investigator at 
(314) 454-8304 and/or the Human Research Protection Office at 1-(800)-438-0445.  
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 
research will be made by Washington University and Incyte.  If you need to seek medical care for a 
research-related injury, please notify the investigator as soon as possible.  
 
HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
Other people such as those indicated below may become aware of your participation in this study and 
may inspect and copy records pertaining to this research.  Some of these records could contain 
information that personally identifies you. We will keep your participation in this research study 
confidential to the extent permitted by law.   
• Government representatives (including the Office for Human Research Protections) to complete 
federal or state responsibilities 
• The U.S. Food and Drug Administration 
• Incyte, manufacturer of itacitinib 
• Your primary care physician if a medical condition that needs urgent attention is discovered 
• Public health agencies to complete public health reporting requirements 
• Hospital or University representatives to complete Hospital or University responsibilities 
• Information about your participation in this study may be documented in your health care records 
and will be available to anyone with access to your health care record, including your health 
insurance company.  This information may also be released as part of a release of information 
request. 
• The last four digits of your social security number may be used in hospital or University systems 
to track billing information for research procedures. 
• Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office. The 
Institutional Review Board has reviewed and approved this study.  
• Other researchers in other laboratories, to conduct research on cancer or other projects; these 
may be individual researchers at other institutions, or they may be other researchers as part of a 
cooperative group. 
• The Quality Assurance and Safety Monitoring Committee at the Siteman Cancer Center for 
auditing purposes 
• The Siteman Cancer Center Clinical Trials Office 
• Any report or article that we write will not include information that can directly identify you.  
The journals that publish these reports or articles require that we share your information that was 
collected for this study with others to make sure the results of this study are correct and help 
develop new ideas for research. Your information will be shared in a way that cannot directly 
identify you. 
• NIH (National Institutes of Health) 
 
To help protect your confidentiality, we will make sure that your study information is kept secure. We 
will keep study information in a secure database that requires a username and password. To help protect 


 
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your confidentiality, no identifying information such as your name, birth date, or social security number 
will be made available to researchers who receive your health information. Furthermore, the study team 
will keep the master code list that links your unique study number with your name and other identifying 
information in locked storage in a locked office (for paper copies) or on a secured network on a 
password-protected computer (for electronic copies). Access to either paper or electronic copies will be 
limited to the Principal Investigator and members of the study team. 
 
The research team will send study results to Incyte.  Information sent to Incyte will be de-identified and 
may be used to analyze the safety and effectiveness of the study medication.  In the future, Incyte may 
continue to use your health information that is collected as part of this study. For example, Incyte may 
combine information from this study with the results of other studies to re-analyze the safety and 
effectiveness of the study medication, to evaluate other products or therapies, to develop a better 
understanding of a disease, or to improve the design of future research studies.  Incyte may also share 
information from the study with regulatory agencies in foreign countries. 
 
If you receive Medicare benefits, are injured as part of your participation in this research study and 
medical treatment relating to this injury is paid by anyone other than you or your insurance company, 
that payer will need to collect personal information about you.  This information includes your name, 
date of birth, gender, social security number, Medicare identification number and information related to 
this research study. The payer will report this information to the Centers for Medicare & Medicaid 
Services (CMS), the federal agency that oversees the Medicare program, during your participation in the 
study and for as long as the payer is required by CMS to report this information.  If you do not want to 
release your personal or treatment related information you have the right to refuse reimbursement by the 
payer for any research injury.  The payer will not use this information for any other purpose. 
 
The Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital 
is supported by funding from the National Cancer Institute (NCI). To meet NCI requirements, your 
protected health information relating to your participation in this study (including your social security 
number) will be stored in a secure database at the Siteman Cancer Center.  This database and also your 
health care records may be reviewed by Siteman Cancer Center personnel.  All information will be 
securely and confidentially maintained.  
 
A description of this clinical trial will be available on http://www.clinicaltrials.gov/, as required by U.S. 
law. This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time. 
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you. PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act). To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form.  The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA.   


 
FOR IRB USE ONLY 
IRB ID #: 201903114 
APPROVAL DATE: 08/13/24 
RELEASED DATE: 08/14/24 
EXPIRATION DATE: 08/12/25 
 
Version 12/8/2023   Expansion Phase 
Page 13 of 15 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law.  When possible, the research team will make sure information cannot be linked to 
you (de-identified).  Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form. If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975.  
 
Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider.  
 
If you decide not to sign this form, it will not affect 
• your treatment or the care given by your health provider. 
• your insurance payment or enrollment in any health plans.   
• any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
If you sign this form: 
• You authorize the use of your PHI for this research 
• This authorization does not expire. 
• You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization).  
• To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of 
the 
Human 
Research 
Protection 
Office 
website 
at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator send you a copy of the letter.    
 
 
 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time. Any data that was collected as 
part of your participation in the study will remain as part of the study records and cannot be removed.   
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify.   
 
What if I decide to withdraw from the study? 
You may withdraw by telling the study team you are no longer interested in participating in the study or 
you may send in a withdrawal letter. A sample withdrawal letter can be found at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ under Withdrawing from a Research 
Study. 
 


 
FOR IRB USE ONLY 
IRB ID #: 201903114 
APPROVAL DATE: 08/13/24 
RELEASED DATE: 08/14/24 
EXPIRATION DATE: 08/12/25 
 
Version 12/8/2023   Expansion Phase 
Page 14 of 15 
If you decide to leave the study early, we will ask you to tell the study doctor if you are thinking about 
stopping so any risks can be evaluated by your doctor. Another reason to tell your doctor that you are 
thinking about stopping is to discuss what follow-up care and testing could be most helpful for you. 
 
Will I receive new information about the study while participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can someone else end my participation in this study? 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned. This might happen for no reason or because staying in the study would be 
harmful, you need treatment that is not allowed while on the study, you fail to follow instructions, you 
become pregnant, or the study is canceled. 
 
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact Dr. Ramzi Abboud at (314) 454-8304.  If you experience a research-related injury, please 
contact Dr. Ramzi Abboud as well; if this is after hours, you will be directed to the exchange number, 
which will be covered by a resident or fellow on call. Please tell this person that you are a research 
participant. 
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office at 1-(800)-438-0445, or email hrpo@wustl.edu.   General 
information about being a research participant can be found on the Human Research Protection Office 
web site, http://hrpo.wustl.edu.  To offer input about your experiences as a research participant or to 
speak to someone other than the research staff, call the Human Research Protection Office at the number 
above. 
 
 
This consent form is not a contract. It is a written explanation of what will happen during the study if 
you decide to participate. You are not waiving any legal rights by agreeing to participate in this study. 
As a participant you have rights and responsibilities as described in this document and including: 
• To be given enough time before signing below to weigh the risks and potential benefits and 
decide if you want to participate without any pressure from the research team or others. 
• To understand all of the information included in the document, have your questions answered, 
and receive an explanation of anything you do not understand. 
• To follow the procedures described in this document and the instructions of the research team to 
the best of your ability unless you choose to stop your participation in the research study. 
• To give the research team accurate and complete information. 
• To tell the research team promptly about any problems you have related to your participation, or 
if you are unable to continue and wish to stop participating in the research study. 
 
 
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201903114 
APPROVAL DATE: 08/13/24 
RELEASED DATE: 08/14/24 
EXPIRATION DATE: 08/12/25 
 
Version 12/8/2023   Expansion Phase 
Page 15 of 15 
Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study.  You will receive a signed and dated copy 
of this form. 
 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 08/12/25. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Participant) 
 
 
 
 
(Date) 
 
 
____________________________________________ 
(Participant's name – printed) 
 
 
 
 
 
Statement of Person Who Obtained Consent 
 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative.  The participant has indicated that they understand the 
risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed)