A Pilot, Prospective, Randomized, Double-Blinded, Vehicle- and Comparator-Controlled Trial on Safety and Efficacy of a Topical Inhibitor of Janus Kinase 1/2 (Ruxolitinib INCB018424 Phosphate 1.5% Cream) for Non-Sclerotic Chronic Cutaneous Graft-Versus-Host Disease
Phase: PHASE2
Conditions: Non-sclerotic Cutaneous Chronic Graft-versus-host Disease
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 1 of 38 
MSK PROTOCOL COVER SHEET 
A Pilot, Prospective, Randomized, Double-Blinded, Vehicle- and Comparator-
Controlled Trial on Safety and Efficacy of a Topical Inhibitor of Janus Kinase 1/2 
(Ruxolitinib INCB018424 Phosphate 1.5% Cream) for Non-Sclerotic and 
Superficially Sclerotic Chronic Cutaneous Graft-Versus-Host Disease (GVHD) 
Principal Investigator/Department: Alina Markova/Medicine 
Memorial Sloan Kettering Cancer Center
IRB Number: 18-412 A(21)
Approval date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
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Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 2 of 38 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ..................................................................... 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .............................................................................. 3 
3.0 
BACKGROUND AND RATIONALE ................................................................................... 4 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ............................................................ 7 
4.1 
Design ............................................................................................................................. 7 
4.2 
Intervention ..................................................................................................................... 8 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ........................................................................... 9 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ......................................................................... 12 
6.1 
Subject Inclusion Criteria ............................................................................................... 12 
6.2 
Subject Exclusion Criteria ............................................................................................. 12 
7.0 
RECRUITMENT PLAN ..................................................................................................... 13 
8.0 
PRETREATMENT EVALUATION .................................................................................... 14 
9.0 
TREATMENT/INTERVENTION PLAN .............................................................................. 15 
10.0 EVALUATION DURING TREATMENT/INTERVENTION ................................................. 17 
11.0 TOXICITIES/SIDE EFFECTS ........................................................................................... 19 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ..................... 24 
13.0 CRITERIA FOR REMOVAL FROM STUDY ..................................................................... 27 
14.0 BIOSTATISTICS .............................................................................................................. 27 
15.0  RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES31 
15.1 Research Participant Registration ................................................................................. 31 
15.2 Randomization .............................................................................................................. 31 
16.0 DATA MANAGEMENT ISSUES ....................................................................................... 32 
16.1 Quality Assurance ......................................................................................................... 32 
16.2 Data and Safety Monitoring ........................................................................................... 33 
17.0 PROTECTION OF HUMAN SUBJECTS .......................................................................... 33 
17.1 Privacy .......................................................................................................................... 34 
17.2 Serious Adverse Event (SAE) Reporting ....................................................................... 34 
17.2.1 ................................................................................................................................... 35 
18.0 INFORMED CONSENT PROCEDURES .......................................................................... 36 
19.0 REFERENCES ................................................................................................................. 37 
20.0 APPENDICES .................................................................................................................. 38 
 
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Page 3 of 38 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
Title: A Pilot, Prospective, Randomized, Double-Blinded, Vehicle- and Comparator-Controlled 
Trial on Safety and Efficacy of a Topical Inhibitor of Janus Kinase 1/2 (Ruxolitinib 
INCB018424 Phosphate 1.5% Cream) for Non-Sclerotic and Superficially Sclerotic Chronic 
Cutaneous Graft-Versus-Host Disease (GVHD). 
 
Total Study Follow-up per patient: 56 days 
 
Schema 
 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
Primary Objective: 
 
To obtain preliminary efficacy estimates of ruxolitinib 1.5% cream for the treatment of 
non-sclerotic and superficially sclerotic chronic cutaneous GVHD at day 28 as 
determined by the body surface area (BSA) of the GVHD rash on the side of the 
face/body treated with topical ruxolitinib cream versus contralateral side treated with 
vehicle at day 28 visit when applied beginning on day 1.  
Secondary Objectives: 
 
To obtain preliminary efficacy estimates of ruxolitinib 1.5% cream for the treatment of 
non-sclerotic and superficially sclerotic chronic cutaneous GVHD at day 28 as 
determined by the Physician’s Global Assessment of Clinical Condition (PGA) of the 
266 patients 
undergo 
alloHCT/year
80/year (30%) 
develop chronic 
GVHD
Enroll n = 24 
patients
Treatment arm 1 (n = 12 patients)
Randomize to topical ruxolitinib BID to 
left side of face/body and topical 
moisturizer BID to right side of 
face/body. 
Treatment arm 2 (n = 12 patients)
Randomize to topical ruxolitinib BID to 
right side of face/body and topical 
moisturizer BID to left side of 
face/body
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GVHD rash on the side of the face/body treated with topical ruxolitinib cream versus 
contralateral side treated with vehicle at day 28 visit when applied beginning on day 1.  
 
To obtain preliminary efficacy estimates of ruxolitinib 1.5% cream for the treatment of 
non-sclerotic and superficially sclerotic chronic cutaneous GVHD at day 28 as 
determined by the objective Composite Assessment of Index Lesion Severity (CAILS) of 
the GVHD rash on the side of the face/body treated with topical ruxolitinib cream versus 
contralateral side treated with vehicle at day 28 visit when applied beginning on day 1.  
 
To obtain preliminary efficacy estimates of ruxolitinib 1.5% cream for the treatment of 
non-sclerotic and superficially sclerotic chronic cutaneous GVHD at day 14 as 
determined by the body surface area (BSA), Physician’s Global Assessment of Clinical 
Condition (PGA), and the objective Composite Assessment of Index Lesion Severity 
(CAILS).  
 
Compare the difference in patient-reported outcomes between the side of the face and 
body treated with topical ruxolitinib cream versus the contralateral side treated with twice 
daily vehicle at day 14 visit and day 28 visit using the adapted National Cancer Institute 
Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse 
Events (PRO-CTCAE™) questionnaire 
 
Compare the difference in chronic cutaneous non-sclerotic and superficially sclerotic 
GVHD BSA between the sides of the face/body treated with topical ruxolitinib and vehicle 
by measuring the agreement of blinded independent physician’s review of standardized 
photography of the right and left sides of the face and body respectively performed at day 
28 visit 
 
Assess the safety and tolerability of topical ruxolitinib by physical examination and 
adverse event reporting 
 
To evaluate accrual, retainment and compliance with therapy  
 
To describe molecular expression profiles of lesional GVHD skin at baseline and after 
treatment with topical ruxolitinib or vehicle moisturizer via minimally invasive skin tape 
strip RNA sequencing  
3.0 
BACKGROUND AND RATIONALE 
Non-sclerotic and superficially sclerotic chronic cutaneous graft-versus-host disease 
(cGVHD) 
In 2016, Memorial Sloan Kettering Cancer Center Bone Marrow Transplantation Service performed 
233 adult and 33 pediatric allogeneic hematopoietic stem cell transplantation (HCTs). Approximately 
30-40% of the unmodified allograft recipients are expected to develop chronic GVHD (cGVHD). The 
skin is the most common site of cGVHD involvement (~75% of patients have cutaneous cGVHD)[1].  
 
Classic chronic GVHD is diagnosed (and distinguished from aGVHD) by the presence of at least 
one diagnostic clinical manifestation (any of: poikiloderma, lichen planus-like features, keratosis 
pilaris-like features, maculopapular rash/erythema, deep sclerotic-like features, morphea-like 
features, lichen sclerosus-like features) OR at least one distinct manifestation (any of: 
depigmentation, sweat impairment, ichthyosis, keratosis pilaris, hypopigmentation, 
hyperpigmentation, etc) confirmed by pertinent biopsy or other relevant test (Table 2). Sclerotic 
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subtypes of chronic cutaneous GVHD includes deep sclerotic and superficially sclerotic subtypes 
(lichen sclerosus-like, morphea-like subtypes). Deep sclerotic cGVHD will be excluded from this 
study. 
 
Chronic GVHD is the leading cause of nonrelapse mortality in patients surviving more than 2 years 
after allogeneic HCT with negative impact on quality of life and long-term outcomes[2]. While 
transplant practices have advanced over the last decades, the incidence and severity of cGVHD 
have continued to rise[2, 3]. Of organs affected by cGVHD, severe skin involvement has increased 
in recent years (from 51% of patients with cutaneous cGVHD at maximum severity in 1999, 65% 
2003, and 71% in 2007[3]. Median onset of cGVHD is 4 to 6 months after allogeneic HCT, with 5-
10% of cases diagnosed beyond 1 year[1]. The clinical manifestations of cGVHD are variable, and 
half of patients have 3 or more involved organs[1]. Median duration of cGVHD treatment is 2-3 
years; however 15% of patients required treatment after 7 years[1].  
 
 
Diagnostic  
(Sufficient to establish 
the diagnosis of 
chronic GVHD) 
Distinctive  
(Seen in chronic GVHD, but 
insufficient alone to 
establish a diagnosis of 
chronic GVHD) 
Other Features 
(Can be acknowledged as part 
of the chronic GVHD 
symptomatology if the diagnosis 
is confirmed) 
Common  
(Seen with both acute 
and chronic GVHD) 
 
Poikiloderma  
 
Lichen planus-
like features  
 
Morphea-like 
features 
 
Lichen 
sclerosus-like 
features  
 
Sclerotic 
features 
 
Depigmentation 
 
Sweat impairment 
 
Ichthyosis 
 
Keratosis pilaris 
 
Hypopigmentation 
 
Hyperpigmentation 
 
Erythema 
 
Maculopapular 
rash 
 
Pruritus 
 
Current treatment recommendations 
To date, there have been no randomized, controlled trials evaluating topical therapies for cutaneous 
cGVHD, nor are there any FDA-approved topical treatments. 
 
Despite this lack of evidence, topical corticosteroids are the mainstay of mild chronic GVHD 
therapy[4-6]. As supported by case reports, topical calcineurin inhibitors (i.e., pimecrolimus cream, 
tacrolimus ointment) are used with variable efficacy in areas at greatest risk for topical corticosteroid 
side effects such as the intertriginous areas and face, as well as for patient who have developed 
steroid dependence[4, 5, 7, 8]. However, in one case series of 18 patients with cutaneous cGVHD 
treated with topical tacrolimus 0.1% ointment twice daily, all patients eventually went on to receive 
more aggressive treatment including increases in steroid dosage, psoralen-ultraviolet-A (PUVA) 
therapy, or extracorporeal photophoresis[7]. Emollients are also recommended as topical 
management for chronic cutaneous GVHD by the Ancillary Therapy and Supportive Care Working 
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Group[4]. For cutaneous cGVHD with extensive body surface area, skin-directed therapies include 
ultraviolet A and narrowband ultraviolet B phototherapy[4], which are associated with increased risk 
for skin cancer (including squamous cell carcinoma, basal cell carcinoma, and melanoma). 
 
Chronic cutaneous non-sclerotic and superficially sclerotic GVHD may be topical- or systemic 
steroid- dependent/ refractory, prompting additional immunosuppressive systemic therapies or 
extracorporeal photophoresis/phototherapy. No topical therapies have been approved, and off label 
use of topical corticosteroids and topical tacrolimus are mainstays of therapy, despite limited efficacy 
and established side effects. Topical corticosteroid use increases risk for development of localized 
infections, striae, skin atrophy/thinning, bruising, acne, discoloration, dependence and with 
widespread use: hyperglycemia, adrenal suppression, and moon-facies [9]. Erythema, burning, 
edema may be experienced on discontinuation of long-term topical steroid use[10]. Half of patients 
experience a burning sensation upon application of topical calcineurin inhibitors.  Given the variable 
efficacy and adverse event profile of currently available topical and systemic therapies for chronic 
cutaneous GVHD, there is an unmet need to have new options for anti-inflammatory treatment in 
this patient population. 
Systemic Janus kinase inhibitors and Graft-versus-host disease 
Janus kinase (JAK) are intracellular nonreceptor tyrosine kinases which play critical functions in T-
cell activation, inflammation, and tissue damage and predicted to be involved in the pathogenesis 
of GVHD [11, 12]. JAK inhibitors,  including ruxolitinib (JAK 1/2 inhibitor) and tofacitinib (JAK 1/3 
inhibitor), inhibit the signal transduction and activation of transcription (STAT) pathway that is 
essential for downstream growth factors and inflammatory cytokines[5].  
JAK inhibitors’ anti-inflammatory properties have been investigated in several immunopathogenic 
disorders. Systemic ruxolitinib is a potent oral selective JAK1/JAK2 inhibitor with equipotent activity 
toward JAK1 and JAK2[12] and has been approved by the FDA for the treatment of intermediate or 
high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis and 
post essential thrombocythemia myelofibrosis, and patients with polycythemia vera who have had an 
inadequate response to or are intolerant of hydroxyurea[12]. Systemic ruxolitinib has demonstrated 
efficacy for management of acute and chronic GVHD in animal models as well as in patients with 
GVHD in several small studies and retrospective clinical reports[11, 12]. However, the systemic use 
of ruxolitinib is associated with several adverse events including anemia, thrombocytopenia, 
neutropenia, liver dysfunction, diarrhea and infection risk that could limit a broader use, particularly 
in allo-HCT recipients with GVHD who commonly have cytopenias, GI and hepatic dysfunction.   
Topical ruxolitinib (JAK 1/2 inhibitor) 
While not commercially available, the topical JAK inhibitors ruxolitinib (JAK 1/2 inhibitor) and 
tofacitinib (JAK 1/3 inhibitor) have been investigated for management of alopecia areata[13], 
vitiligo, psoriasis and atopic dermatitis with efficacy[14-16].  
In patients with active psoriasis, topical ruxolitinib (INCB018424) 1.5%  cream twice daily for 28 days 
was pharmacologically active, modulated proinflammatory cytokines, and was well tolerated; 
treatment resulted in improvements in psoriasis lesion scores[17]. No significant inhibition of 
pSTAT3 in peripheral blood cells was observed following topical application, consistent with the 
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generally low steady-state plasma concentrations of INCB018424 measured[17].  A 20-week, 
open-label, proof-of-concept trial of twice daily topical ruxolitinib 1.5% cream in 12 patients provided 
significant repigmentation in facial vitiligo[18]. A topical JAK/spleen tyrosine kinase (SYK) dual 
inhibitor has demonstrated efficacy for ocular GVHD with a higher mean decrease in total corneal 
fluorescein staining in the group treated with an ophthalmic JAK/SYK solution  as compared to the 
vehicle-treated group at 12 weeks [19]. 
 
Topical ruxolitinib and chronic cutaneous non-sclerotic and superficially sclerotic GVHD 
Given efficacy of ruxolitinib with oral use in GVHD and with topical use in other dermatoses, we 
hypothesize topical ruxolitinib may be used for the treatment of chronic cutaneous (non-sclerotic) 
and superficially sclerotic (lichen sclerosus-like; morphea-like) GVHD and will be more effective in 
decreasing the body surface area of chronic cutaneous GVHD when compared to topical vehicle. 
 
Of note, topical ruxolitinib treatment in a murine model of skin GVHD was associated with less 
severe skin GVHD scores, reduced T-cell infiltration of the skin and maintenance of LGR5+ hair 
follicle stem cell levels that are normally reduced with the onset of GVHD[12, 20, 21]. Skin GVHD 
targets Lgr5+ hair follicle stem cells in association with impaired hair regeneration and wound 
healing[20]. Topical ruxolitinib, unlike corticosteroids, protects Lgr5+ skin stem cells and maintains 
skin homeostasis in skin GVHD[20]. 
 
This study utilizes a novel method of delivery and active agent for the topical treatment of cutaneous 
GVHD, potentially expanding the therapeutic options for patients with GVHD. Topical ruxolitinib 
would augment the armamentarium of agents available to treat these patients, without resorting to 
systemic immunosuppressive therapies, nor causing side effects of skin atrophy, bruising, and 
tachyphylaxis due to topical steroids. 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
4.1 
Design 
Design: This is a prospective, randomized double-blinded, vehicle- and comparator- 
controlled pilot study followed by an open label extension for all patients who wish to 
continue on study 
 
Purpose: This study was designed to test the safety and efficacy of topical ruxolitinib in 
treating non-sclerotic and superficially sclerotic chronic cutaneous graft-versus-host disease.  
 
Patient population: Male or female patients 12 years or older with clinically or histologically 
confirmed non-sclerotic chronic and superficially sclerotic cutaneous graft-versus-host 
disease after allogeneic hematopoietic stem cell transplantation.  
 
Study duration: The study will span 28 ± 3 days. An end of study visit will occur on the last 
day of topical therapy day 28 ± 3 days, followed by a safety visit 4 weeks later (day 56 or 84). 
All eligible patients determined by the attending dermatologist at day 28 will be given the 
opportunity to continue topical ruxolitinib for an additional 28 days.  Safety follow-up will 
continue for an additional 28 days (day 84).  In general, each participant will be followed for 
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up to 28 ± 5 days (day 56 or 84) following the last dose of study therapy, and the study is 
expected to meet accrual goals over a period of 6-24 months. Data analysis will take an 
additional 12 months, making the total duration of the study 3 years. The first interim data 
analysis will occur after the study has accrued 10 evaluable participants. Only the 
biostatician and Dermtech personnel will be unblinded during the analysis. The second 
interim data analysis will occur with the remaining 14 evaluable participants. Only the 
biostatician and Dermtech personnel will be unblinded during the analysis. 
 
 
4.2 
Intervention 
Lesional areas will be chosen by the attending dermatologist. Lesional areas of the same 
corresponding size on the left and right hand sides of the participant will be evaluated, 
demarcated, imaged. In this study, participants will provide both treatment and vehicle 
control lesions. Eligible patients will be randomized to one of two treatment groups: Group 1 
will be randomized to topical ruxolitinib BID to left side of face/body and topical moisturizer 
BID to right side of face/body; Group 2 will be randomized to topical ruxolitinib BID to right 
side of face/body and topical moisturizer BID to left side of face/body. Randomizing the 
treatment side is to maintain blinding of the physician. For example: if patients are all 
assigned to apply topical ruxolintib to their right side and are showing clinical improvement 
on each patient’s right side consistently, the physician will be aware that the right side is the 
treated side, possibly adding bias to the study. Variability in application side will also help to 
account for inter-patient variability in application with right- versus- left hand. Participants and 
their study doctor will be blinded from knowing which side of the face/body will be treated 
with the study cream, and which side of the face/body will be treated with the vehicle. For 
study purposes, Study Day 1 is defined as the first day of topical application. Patients will 
self-administer topical ruxolitinib and vehicle topically to affected rash area on directed side 
of face/body and record topical application on study diaries that will be provided by the study 
doctor or a member of the research team. On Study Day 28, end of treatment day, all 
patients will be eligible for the open label portion of the study. The attending will determine 
the patient's response, and if the patient wishes to continue, then they will be given the 
opportunity to use the topical ruxolitinib for an additional 28 days. If the patient wishes to 
continue then pharmacy will dispense open label ruxolitinib for the patient to apply to both 
sides of the body, not to exceed 20% total BSA. The PI, the Clinical Research Coordinator, 
and the patient will remain blinded to the initial treatment arm, but will become unblinded 
during the open label portion." 
Topical ruxolitinib 1.5% cream:  After gently washing skin and patting dry, the patient will 
apply thin layer in morning and at least 60 minutes before bedtime to one side of face/body. 
The patient will wash hands after application. (If caregiver is applying creams, he/she should 
wear nitrile gloves prior to application and discard after each cream use.) 
Patients will be instructed to wash hands between applications of each cream. 
Topical vehicle/moisturizer cream:  After gently washing skin and patting dry, the patient 
will apply thin layer in morning and at least 60 minutes before bedtime to contralateral side of 
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face/body. The patient will wash hands after application. (If caregiver is applying creams, 
he/she should wear nitrile gloves prior to application and discard after each cream use.) 
At initial study visit, BSA of the rash will be calculated, and all patients will be directed to 
apply a dose of cream based on BSA involved (same BSA will be used for treatment and 
placebo sides). For each side at this initial study visit, the skin area targeted for treatment will 
be outlined with surgical marker, photographed, and a photograph of each outlined target 
treatment area will be provided to the patient as an application reference. After BSA 
calculation at initial visits, patients will all be required to apply each cream to lesional skin as 
directed based on body surface area (1 adult fingertip unit (FTU) = 0.5g = ~ 2% BSA). 
Patients can apply a maximum of 10 adult fingertip units (5 grams; total maximum daily dose, 
10 grams) of topical ruxolitinib 1.5% cream onto the randomized side of face/body and an 
equivalent amount of the vehicle to the contralateral side of face/body in morning and prior to 
bedtime, on Days 1-28 (56 applications).  
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
  
5.1 Study drug, packing, and labeling  
The study drug to be used in the course of this study is INCB018424 (ruxolitinib) phosphate 
cream.  
 
INCB018424 Phosphate Structural Formula: 
 
 
Physical Properties: INCB018424 phosphate drug substance is a white to off-white to light 
pink powder. 
 
Chemical Properties: The chemical name of INCB018424 phosphate is (R)-3-(4-(7H-
pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate. 
INCB018424 phosphate has a molecular formula of C17H21N6O4P and a molecular weight 
of 404.36. 
 
INCB018424 phosphate cream is a topical formulation of an investigational product under 
development for the treatment of patients with psoriasis, alopecia areata (AA), atopic 
dermatitis (AD), vitiligo, and other potential autoimmune diseases of the skin. INCB018424 
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phosphate (ruxolitinib) is an inhibitor of the JAK family of protein tyrosine kinases. Mitogenic 
and inflammatory cytokines are strongly implicated in the pathogenesis of psoriasis, AA, AD, 
and other potential autoimmune diseases of the skin. Inhibition of specific cytokine function 
using antibodies directed against the common p40 subunit of IL-12 and IL-23 has 
demonstrated proof-of-concept validating cytokine signaling as a therapeutic target for the 
treatment of psoriasis. Oral treatment with JAK inhibitors has been shown to benefit patients 
with AA. Because JAKs serve to translate extracellular signals from a number of relevant 
cytokines and growth factors upregulated in inflammatory diseases such as psoriasis, AA, 
AD, and other potential autoimmune diseases of the skin, JAK inhibitors represent potential 
therapeutic agents for these disease states.  
An oral formulation of INCB018424 phosphate has been clinically evaluated for the treatment 
of patients with myeloproliferative diseases, hematologic malignancies, and solid tumors and 
is currently approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV) in 
multiple countries. In addition to the safety pharmacology and toxicology studies that were 
completed to support development of INCB018424 phosphate cream, the toxicologic and 
toxicokinetic profiles of INCB018424 phosphate have also been characterized following oral 
administration. 
 
INCB018424 represents a novel, potent, and selective inhibitor of the JAKs. INCB018424 
potently (IC50 < 5 nM) inhibits JAKs, yet it does not significantly inhibit (< 30% inhibition) a 
broad panel of 26 kinases when tested at 200 nM (approximately 100× the average IC50 
value for JAK enzyme inhibition). Moreover, in cell-based assays relevant to the 
pathogenesis of psoriasis, such as IL-2–stimulated phosphorylation of STATs and IL-2–
induced proliferation of T cells, INCB018424 demonstrates excellent potency (IC50 values of 
10-40 nM). This effect was not due to general cytotoxicity because INCB018424 (up to 10 
μM) had no effect on the survival of resting T cells (without IL-2 stimulation). INCB018424 
also potently inhibited the phosphorylation of STAT proteins and the production of 
proinflammatory factors induced by cytokines such as IL-23 and IFN-γ. Topical application of 
INCB018424 demonstrated excellent efficacy in an in vivo model of immune-based skin 
inflammation, the delayed-type hypersensitivity (DTH) model in mice, including reduced ear 
swelling, reduced immune cell infiltrates, and normalization of tissue histology. Further, 
INCB018424 was also efficacious in the inflammatory phase of the dorsal DTH model when 
applied in a clinically relevant cream formulation. In summary, pharmacological data obtained 
with in vitro and in vivo model systems supports the potential utility of topically applied 
INCB018424 in the treatment of psoriasis. 
 
Formulation: INCB018424 phosphate cream has been formulated in 4 strengths (0.15%, 
0.5%, 1.0%, and 1.5% w/w free base equivalent) that are actively being investigated. All 
excipients in both the INCB018424 and vehicle cream formulations are compendial grade or 
are approved for use in topical products. The matching vehicle cream is an identical 
formulation to the active product except for the absence of drug substance. 
 
 
Labeling: To help ensure blinding, tubes of ruxolitinib and moisturizer will be labeled by 
pharmacy. The pharmacist will tear off a perforated label section with randomization group, 
before dispensing to the patient. Medication labels will comply with US legal. They will supply 
no information about the patient. The same storage conditions will be described on each 
medication label.  If the patient decides to continue the treatment after day 28,  the pharmacy 
will label the drug based on the labels provided by Incyte.  
 
5.2 Drug supply and storage  
 
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The drug will be shipped by Incyte Corporation directly to the MSKCC pharmacy. It will be 
received by a designated person at the MSKCC pharmacy, handled and stored properly and 
safely, and kept in a secured location to which only the investigator/pharmacist and/or 
designated assistants will have access. Upon receipt, INCB018424 phosphate cream and 
vehicle should be stored according to the instructions specified on the drug labels [Store at 
15°C to 30°C (59°F to 86°F). These instructions will also be made clear to the patient for 
storage and self-administration of ruxolitinib at home (Patient information sheet, Appendix 
VI). Upon registration of a new study participant, MSKCC pharmacy will clearly label the two 
study creams (ruxolitinib and vehicle) according to which side of the body each cream should 
be applied based on the patient’s randomized treatment arm.  
 
At their baseline visit, patients will receive two 45gm tube(s) of topical ruxolitinib phosphate 
cream, 1.5% and two 45gm tube(s) of the vehicle as indicated by their involved BSA. An 
additional tube of each cream will be made available to the patient, after using up the initial 
tube (as per study instructions) and returning the empty tube to the study staff.  
 
At their Day 28 visit, patients who wish to continue on study will receive a tube of the 
treatment. The pharmacy will dispense open label ruxolitinib for the patient to apply to both 
sides of the body, not to exceed 20% total BSA, for an additional 28 days. 
 
Study drug may be dispensed in real time or shipped to patients for the initial dispensation. 
Patients will not be charged for the shipment of the drug.  
 
5.3 Study drug compliance 
Compliance will be assessed by the investigator and/or study personnel at each patient visit 
using information provided by the patient and/or caregiver in the Medication Application Diary 
(Appendix VII). This record will capture information of medication used, dosages 
administered, and intervals between visits and the completion of the study. Patient is 
required to bring both vehicle and control tubes to study visits for drug diary review and drug 
accountability return. Patients in the open label extension and optional extension period will 
be required to bring in the ruxolitinib tube to study visits. For both the open label extension 
and optional extension portions of the study, the patient does not have to fill out a drug diary. 
Re-consent is required for the optional extension period to ensure that the participant agrees 
to continue treatment with ruxolitinib study drug.  
 
5.4 Ruxolitinib cream administration  
All participants will initiate treatment within 7 days of informed consent/ registration 
(exceptions can be made per PI discretion). The ruxolitinib cream will be administered each 
day in the morning and before bedtime for the entire course of treatment. Only on Day 1, 
application of the first dose of study medication will be done preferably by the research 
physician with use of nitrile gloves—subsequently, the medication will be self-administered 
twice each day by the patient (or caregiver), as per the instructions provided. Nitrile gloves 
will be worn by caregiver for any caregiver-administered applications. 
 
5.5 Supportive care guidelines and concomitant medications  
 
Participants must be instructed not to apply any (new) topical additional medications, 
including over-the-counter products during the trial without prior consultation with the 
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investigator. All topical products applied to the skin within 14 days of screening should be 
recorded. This includes all moisturizers, sunscreen, sunblock etc. If concomitant therapy 
must be added or changed, including over-the-counter medications, or alternative therapies, 
the reason and name of the drug/therapy should be recorded by the investigator.  
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY 
Any patients age 12 years and older with clinical or histologically confirmed non-sclerotic or 
superficially sclerotic chronic cutaneous graft-versus host disease after allogeneic 
hematopoietic stem cell transplantation will be considered for protocol participation. 
 
6.1 
Subject Inclusion Criteria 
 
Patients (≥ 12 years)  
 
History of allogeneic hematopoietic stem cell transplantation 
 
BSA of at least 2% of clinically or histologically confirmed non-sclerotic or superficially 
sclerotic cutaneous chronic graft-versus-host disease (diagnosed and BSA calculated in 
accordance with the National Institutes of Health Chronic Graft-versus-Host Disease 
Consensus for Clinical Trials: I. The 2014 Diagnosis and Staging Working Group Report) 
 
Patients age ≥ 18 years must provide written informed consent; or patients age ≥12 years 
and <18 years must provide assent and have at least one guardian provide written 
informed consent to participate in the study. 
 
 Able to self-administer topical interventions or provide for another person to apply the 
topical interventions (while wearing nitrile gloves) 
 
If on systemic therapy for GVHD, systemic therapy must be stable for past 4 weeks; 
however, any planned systemic corticosteroid taper during the study will be permitted. 
Changes in systemic therapy during the study period will be allowed for the management 
of non-skin GVHD. 
 
Any concurrent topical therapies including topical corticosteroids, topical calcienurin 
inhibitors, moisturizers, phototherapy (narrowband UVB or UVA1); or excimer laser 
therapy must be discontinued on Study Day 0. 
   
6.2 
Subject Exclusion Criteria 
 
Known history of allergy to any ingredient of the study medication  
 
Patients with deep sclerotic cutaneous graft-versus-host disease including deep sclerotic 
subtypes of chronic cutaneous GVHD 
 
Use of concurrent topical therapy including topical corticosteroids, topical calcienurin 
inhibitors, moisturizers, phototherapy (narrowband UVB or UVA1); or excimer laser 
therapy after Study Day 0 up to and including Study Day 28. 
 
Changes in systemic therapy during study period for the purpose of treating skin GVHD. 
 
Special populations: 
o vulnerable populations e.g. decisionally impaired (cognitive, psychiatric), 
terminally ill, prisoners  
o patients who, in the opinion of the investigator have a condition that precludes 
their ability to provide an informed consent  
 
Concurrent participation in another topical trial of a drug(s) or medical device, or the 
subject is in an exclusion period after a previous trial of drug(s) or medical device  
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 
Pregnancy or lactation  
 
Patients with inadequate liver function (ALT above 4 × upper limit of normal [ULN] for the 
patient’s age or direct bilirubin 4 × ULN for the patient’s age and the laboratory 
abnormalities are considered to be due to underlying liver dysfunction) unless attributed 
to GVHD (if direct bilirubin is not in the medical record, it is acceptable to use total 
bilirubin x4 ULN).  
 
Active uncontrolled infection requiring systemic therapy. Subjects with a controlled 
infection receiving definitive therapy for 48 hours prior to enrollment are eligible. 
 
7.0 
RECRUITMENT PLAN 
A member of the patient’s treatment team, a protocol investigator, or research staff, at Memorial 
Sloan Kettering Cancer Center (MSKCC) will identify potential research subjects. If the investigator 
is a member of the treatment team, s/he will screen their patient’s medical records for suitable 
research study participants and discuss the study and their potential for enrolling in the research 
study. Potential subjects may also be referred to the investigator/research staff of the study by the 
treating physician or any MSKCC physician. Patients may also be referred from physicians at 
Hackensack Medical Center for participation in this study. Generally, the patient’s primary 
hematologist and primary dermatologist will identify potential research subjects.  
 
The participating investigators may also screen the medical records of patients with whom they do 
not have a treatment relationship for the limited purpose of identifying patients who would be eligible 
to enroll in the study, and to record appropriate contact information in order to approach these 
patients regarding the possibility of enrolling in the study. 
The following procedure will be employed in enrolling all participants into the study. (Potentially) 
eligible patients identified by the mechanism described in the preceding paragraphs, will be offered 
participation in the study. This will be accomplished by the treating physician, clinician, or research 
staff, in person. The purpose of the study will be explained to the patient and informed consent will 
be obtained from willing participants. Potential participants will also be offered the opportunity to 
consider participation and review the consent documents (e.g. at home) with the option of providing 
consent in the future. Subsequently, a consenting professional will call potential adult study 
participants to invite them to participate. For potential pediatric patients, a parent will be contacted to 
see if their child would like to participate. If they agree, then the eligible participants will be 
scheduled for in-person consenting and eventual baseline assessments. This visit will preferably 
coincide with patients’ standard-of-care visit. Potential participants who decline participation will not 
be contacted again for the purpose of recruitment into the study.  
We will only retain participants’ basic information (e.g. questionnaire responses, eligibility checklist, 
etc.) that is needed for study reporting purposes. These records will be maintained on a secured 
Dermatology shared drive. We will also maintain a list of all participants approached throughout the 
entire study to record reasons for refusal and avoid re-approaching healthy volunteers that have 
been identified as ineligible or refusing participation. This list will be destroyed at the completion of 
the study.  
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The investigators participating in this research include physicians and research staff from Memorial 
Sloan Kettering Cancer Center, as listed on the face page of this protocol, who have successfully 
completed training for protection of human research subjects in compliance with MSKCC clinical 
research policy. Written consent will be obtained by one of these individuals or his/her designee, 
who must also have successfully completed training for protection of human subjects in compliance 
with MSKCC clinical research policy.  
During the initial conversation between the investigator/research staff and the patient, the patient 
may be asked to provide certain health information that is necessary to the recruitment and 
enrollment process. The investigator/research staff may also review portions of their medical records 
at MSKCC in order to further assess eligibility. They will use the information provided by the patient 
and/or in the medical record to confirm that the patient is eligible, and to contact the patient 
regarding research enrollment. If the patient turns out to be ineligible for the research study, the 
study personnel will destroy all information collected on the patient during the initial conversation 
and medical records review, except for any information that must be maintained for screening log 
purposes.  
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment team. 
The recruitment process outlined presents no more than minimal risk to the privacy of the patients 
who are screened and minimal PHI will be maintained as part of a screening log. For these reasons, 
we seek a (partial) limited waiver of authorization for the purposes of (1) reviewing medical records 
to identify potential research subjects and obtain information relevant to the enrollment process; (2) 
conversing with patients regarding possible enrollment; (3) handling of PHI contained within those 
records and provided by the potential subjects; and (4) maintaining information in a screening log of 
patients approached (if applicable). 
 
8.0 
PRETREATMENT EVALUATION 
Patients may be screened and consented starting from up to 7 days before study initiation. 
The following initial baseline procedures can take place at any time during this period, or on the day 
of initiation (Day 1)   
 
1. Medical history, including concomitant medications  
2. Study assessments (serve as baseline measures for the study):  
 
Patient-reported Outcomes (Appendix III):  
o Adapted PRO-CTCAE™ for each side of face/body affected by GVHD 
rash 
 
Clinical assessments (Appendices I, II, IV, V) 
o Skin examination with calculation of body surface area (BSA), Physician’s 
Global Assessment of Clinical Condition (PGA), and the objective 
Composite Assessment of Index Lesion Severity (CAILS) for each side 
 
Standardized photography and 3D photography  
o During the first and third study visit, if the participant gives consent, the 
research photographer will take 3D photography, also called Total Body 
Photography of the patient.  
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o For each side, the skin area targeted for treatment will be outlined with 
surgical marker, photographed, and a photograph of each outlined target 
treatment area will be provided to the patient as an application reference. 
 
Laboratory investigations 
o Laboratory analyses and skin biopsy will be performed only as clinically 
indicated for routine care.  
o Minimally invasive skin tape strip RNA sequencing will be performed on 
each face/body side by the study dermatologist (Appendix VIII) 
 
Visit # 
Study day: 
Pre-study Screening or 
Day 1 
Reason for visit 
Informed consent 
X 
Medical history 
X 
Pregnancy test (if applicable for 
females of child-bearing 
potential) 
X 
Clinical assessment (i.e., BSA, 
PGA, and CAILS on each side; 
adverse events/CTCAE 
assessment) 
X 
Skin examination 
X 
Lesional skin tape stripping on 
each side 
 
Patient-reported outcomes 
questionnaire for each side 
X 
Standardized photography 
X 
Drug application 
X 
Drug diary return 
X 
Drug accountability 
X 
 
 
9.0 
TREATMENT/INTERVENTION PLAN 
Patients will be prescribed twice daily use of topical ruxolitinib 1.5% cream (randomized half of 
face/body) and vehicle/moisturizer (for contralateral side of face/body) to a maximum of 20% BSA 
on each side for 28 ± 3 days. Topical ruxolitinib will be provided as topical cream.  
In the morning and evening (at least 60 minutes before bedtime), patients will be instructed to apply 
a pre-designated number of fingertip units of each topical intervention (ruxolitinib and moisturizer) to 
each side of the face/body unit as outlined in provided photograph for each side. Patients will 
receive detailed instructions at the baseline visit and receive clear, written instructions on the 
standarized application technique (see Patient Instructions: Topical Medications). Patients will apply 
topical ruxolitinib cream and vehicle cream to the equivalent BSA on each side (e.g., if one side has 
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15% lesional skin and contralateral side has 10% lesional skin, the subject will treat only 10% on 
each side) and no more than to 20% BSA on each side. 
Before topical applications, patients will be instructed to gently wash the face and body with a gentle 
cleanser (examples include Cetaphil, Purpose, Aveeno, Vanicream products) and pat skin dry with a 
clean towel. Patients will not be encouraged to apply topical emollients to the treated face and body 
during the study, but if desired, they may apply to untreated areas. Patients will be advised not to 
use products with chemicals or perfumes.  
We do not anticipate the need for any adjustments to the treatment plan as consequence of adverse 
reactions to ruxolitinib (see section 11.0), but any patients with adverse cutaneous reactions to 
treatment with topical ruxolitinib 1.5% cream, or moisturizer will be advised to return to clinic to see a 
dermatologist right away. Adverse event reporting will be based on CTCAE v5.0, as applicable[22].  
In the event of a patient emergency, the principal investigator and study pharmacist will be able to 
unblind the patient. 
All patients will be advised to follow photo-protective measures during the study, and avoid 
unnecessary sun exposure. Daily sunscreen use will not be recommended, because the effect on 
topical ruxolitinib activity is unknown. Instead, when outside, patients should be careful to wear 
clothing that protects as much of their skin as possible, as well as hats with wide brims to protect the 
face. Patients will also be asked to use a diary to improve their compliance with the application of 
topical ruxolitinib 1.5% cream/vehicle to unilateral sides of the face and body, as well as to record 
any adverse effects of treatment, and will be asked to bring diaries to all patient visits. Patients will 
be allowed to continue applying topical ruxolitinib 1.5% cream to both sides of the face and body 
(≤20% BSA) for another 28 ± 3 days after the completion of the study (day 28 ± 3 days) if they have 
a partial or complete response during the treatment portion of the study.   
Skin examinations will be part of the evaluation performed during baseline visit at day 1, day 14, day 
28, and day 56 visits; as well as day 84 visit for those patients who repeat a subsequent topical 
ruxolitinib 28-day course. Patients will also complete adapted PRO-CTCAE™ questionnaires to 
measure dermatology-specific patient-reported symptoms and outcomes at each of the 
aforementioned visits for each side of the face/body. Study questionnaires should take the 
participant no more than 10 minutes to complete at each time point. Standarized photography will be 
performed on , day 1, day 14 ± 3 days, day 28 ± 3 days, day 56 ± 5 days, and day 84 ± 5 days for 
those patients who repeat a study drug course. Total body photography will be perfomed on day 1 
and day 3, if participant consents. Patients will be seen in the BMT clinics, and their clinical 
response will be assessed in the Dermatology clinic of Memorial Sloan-Kettering Cancer Center 
located in Manhattan.  
9.1 Treatment period extensions 
After completion of the open-label portion of the study, interested subjects may continue to 
participate on the Treatment Extension with topical ruxolitinib cream as long as they meet 
criteria* to continue to receive therapy, tolerate the treatment regimen, do not discontinue 
topical ruxolitinib, do not withdraw consent, or until topical ruxolitinib becomes commercially 
available for the treatment of cutaneous graft-versus-host disease. Subjects who continue on 
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the treatment period extension, will have a safety follow-up visit 28 days after completion of 
therapy. Visit 5 will be replaced by Visit 6 for participants who enroll in the extension period. 
Re-consent is required to be obtained on Visit 4 for the optional extension period to ensure 
that the particioant agrees to continue treatment with ruxolitinib study drug.  
 
*However, subjects who participate in the treatment period extension are permitted to use other 
topicals and/or phototherapy concurrently. 
 
10.0 EVALUATION DURING TREATMENT/INTERVENTION 
 Table 1. Assessments: 4 to 5 study visits 
Visit # 
Pre-study 
1 
2 
3 
4 
5 
6 
Study Day 
Day -7 to 
Day 0 
Day 1 
Day 14 ± 3 
days 
Day 28 ± 3 
days 
Day 56 ± 5 
days 
Day 84 ± 5 
days 
28 Days ± 
5 days 
after 
treatment 
completion 
Reason for 
visit 
Screening 
Pre-
treatment 
baseline 
evaluation 
Interval follow-
up evaluation 
Blinded 
Treatment 
ends 
Safety 
follow-up 
visit/Open 
label 
extension 
follow-up 
evaluation 
Open-label 
extension 
safety 
follow-up 
visit 
Safety 
follow-up 
visit after 
treatment 
extension 
period 
ends 
Informed 
consent 
X 
 
 
 
X**** 
 
 
Medical 
history 
X 
 
 
 
 
 
 
Pregnancy 
test (if 
applicable for 
females of 
child-bearing 
potential) 
X 
 
 
X 
 
 
 
Clinical 
assessment 
(i.e., BSA, 
PGA, and 
CAILS on 
each side; 
adverse 
events/CTCAE 
assessment) 
 
X 
X 
X 
X 
X 
 
 
 
X 
Skin 
examination 
 
X 
X 
X 
X 
X 
X 
Lesional skin 
tape stripping 
on each side 
 
 
 
X 
 
 
 
Patient-
reported 
outcomes 
 
X 
X 
X 
X 
X 
X 
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Page 18 of 38 
questionnaire 
for each side 
3D 
Photography**  
 
X 
 
X 
 
 
 
Standardized 
photography 
 
X 
X 
X 
X 
X 
X 
Drug 
application 
 
X 
X 
X 
X***  
 
 
Drug diary 
return 
 
 
X 
X 
 
 
 
Drug 
accountability 
 
 
X 
X 
X*** 
 
 
 
* Day 1 assessments can also be done at day 0 
** Optional for the study. Participant does not need to complete in order to participate on the study. 
*** For those patients who enroll onto open label portion, but do not enroll into the extension period of the 
study: patients apply study drug up to Visit 4 but not after this visit. Patients who enroll into the extension 
period will continue to apply drug until they withdraw from the extension period. 
****For patients who enroll into treatment extension period. 
 
For study purposes, Study Day 1 is defined as the first day of topical application.  
 
10.1 Clinical  
All study assessments/ procedures will be obtained in the course of routine outpatient dermatologic 
care. Therefore, this study places minimal burden on the patient. 
Patients will receive evaluation in the Dermatology outpatient clinic of Memorial Sloan Kettering 
Cancer Center located in Manhattan. The medical history and other relevant details (demographics, 
concomitant medications) will be obtained as listed in Table 1. Patients will start treatment to an 
equivalent body surface areas to each side with ruxolintib cream to the designated affected side and 
vehicle cream to the contralateral side. Following the start of application of topical ruxolintib cream, 
patients will be seen by a physician and research staff for interim medical history, concomitant 
medications, study assessments, and AEs, on days 1, 14, 28, 56, ± 84. 
 
10.2 Study Assessments  
The subjects will be assessed by the study dermatologist on day 0,1, 14, at the end of study day 28 
days, at the safety visit 4 weeks later (day 56), as well as 28 days after last dose of study drug for 
subjects who continue in the open-label extension (day 84). The assessments will include (Table 1): 
 
Clinical assessment:  
 
Skin examination with calculation of: 
o Lesional Body Surface Area: As per the 2014 NIH consensus criteria for chronic 
GVHD: Body surface area calculation of each face/body side that will be targeted with 
topical therapy will be performed by the study dermatologist  on study visit on day 1, 
14 ± 3 days, 28 ± 3 days, 56 ± 5 days[, and day 84 ± 5 days for subjects who 
continue in the open-label extension]. Patient will be photographed, and subsequently 
treatment-targeted BSA will be additionally calculated from these study visit photos by 
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one bone marrow transplantation hematologist blinded to treatment side. 
Standardized photography will be performed at each evaluation visit. (Table 1, 
Appendix I-II). Marked treatment areas will not change if improvement or worsening is 
seen. 
o Physician’s Global Assessment of Clinical Condition (PGA): area calculation of 
each face/body side will be performed by the study dermatologist  on study visit on 
day 1, 14 ± 3 days, 28 ± 3 days, 56 ± 5 days [, and day 84 ± 5 days for subjects who 
continue in the open-label extension] (Appendix IV) 
o Composite Assessment of Index Lesion Severity (CAILS) for each side: area 
calculation of each face/body side will be performed by the study dermatologist  on 
study visit on day 1, 14 ± 3 days, 28 ± 3 days, 56 ± 5 days[, and day 84 ± 5 days for 
subjects who continue in the open-label extension]  (Appendix V) 
o Adverse events will be assessed and graded as per the Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0, and as applicable. 
 
Patient-reported outcomes assessment: Patients will complete an adapted skin-specific 
PRO-CTCAE™ on study visit on day 1, 14 ± 3 days, 28 ± 3 days, 56 ± 5 days[, and day 84 ± 
5 days for subjects who continue in the open-label extension]  for each side of the face/body 
(two questionnaires in total per visit). (Table 1, Appendix III). This questionnaire should take 
patients less than 10 minutes to complete.  
 
Safety follow-up: After completion of the 28 day ± 3 days study interval, patients will return 
for a final safety and follow-up visit at day 56 ± 5 days. Additionally, any patients who repeat 
a study drug course will return for an additional safety visit at day 84 ± 5 days. At this visit, 
patients will have a safety evaluation for possible adverse events (Table 1). 
 
Diagnostic interventions: Laboratory analyses and skin biopsy will be performed as 
clinically indicated. Minimally invasive skin tape strip RNA sequencing will be performed on 
each face/body side by the study dermatologist on study visit on day 28 ± 3 days. These skin 
strips will be shipped to DermTech, Inc. (11099 N. Torrey Pines Rd, Suite 100, La Jolla, CA 
92037)  Appendix VIII) 
 
Compliance with the topical agent will be assessed by reviewing the patient’s application 
diary (Appendix VII). 
 
11.0 TOXICITIES/SIDE EFFECTS 
Topical ruxolitinib (INCB018424) 1.5% cream application results in a markedly (~90%) lower relative 
bioavailability than that following oral administration[23]. 
INCB018424 tested positive in a photoclastogenicity assay, hence there may be a risk of skin 
reaction to the combined exposure of INCB018424 and sunlight[23]. Subjects should be cautioned 
to avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun 
lamps, etc), and when outdoors, should be advised to wear loose-fitting clothing that protects the 
treated area from the sun[23].  
The primary clinical risks noted with orally administered INCB018424 (ruxolitinib) treatment are the 
potential sequelae of decreased hematopoietic proliferation secondary to the inhibition of growth 
factor pathways by JAK2 antagonism[23]. Systemic exposure with topical INCB018424 is several 
fold below that which is associated with hematologic changes that may be seen following oral 
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dosing[23]. Dose-dependent, reversible thrombocytopenia has been observed in subjects with MF 
who were treated orally with ruxolitinib, as well as anemia and risks of possible transfusion, and less 
frequently neutropenia. An increased rate of infection is an additional potential risk of 
immunomodulation. GI side effects including diarrhea, nausea and liver dysfunction have been 
reported with oral Ruxolitinib. A few subjects have had an apparent worsening of their premorbid 
disease symptoms following rapid cessation of oral ruxolitinib therapy for MF[23]. A gradual tapering 
and use of steroids in fragile patients may be considered when stopping oral ruxolitinib therapy[23]. 
Leukemic transformation has been observed, but was considered to be consistent with the natural 
history of the underlying disease and unrelated to drug. In healthy volunteers and RA patients with 
greater bone marrow reserve, the effects on hematopoietic proliferation appear to be less 
pronounced[23].  
INCB018424 phosphate cream has been evaluated topically in over 350 subjects in 6 clinical studies 
with administration of 1 to 24 months in duration[23].  
Topical INCB018424 [23] 
Study INCB 18424-201: In the topical proof-of-concept study in 29 subjects with psoriasis, 47 TEAEs 
were reported by 18 subjects. No deaths or other SAEs occurred. No subjects experienced life-
threatening AEs or were discontinued from study drug or the study due to an AE. Pruritus and dry 
skin were the AEs reported by the greatest number of subjects (3 and 4 subjects, respectively). 
Cutaneous AEs were seen with similar frequency for vehicle-treated lesions and active comparator 
treated lesions when compared with INCB018424-treated lesions. All TEAEs resolved except 1 of 
QTcF prolonged, which began 14 days after the last application of study medication and was 
assessed as ongoing at the follow-up visit.  
Application of INCB018424 0.5% to 1.5% cream QD or BID resulted in mean plasma 
concentrations of INCB018424 ranging from 0.34 ± 0.4 nM (Cohort A) through 2.10 ± 1.78 nM 
(Cohort C) at steady state. The mean INCB018424 steady-state concentration increased 
approximately proportional to application dose per day. The size of the lesion areas treated 
ranged from 9 to 63 cm2. Application of INCB018424 0.5% to 1.5% cream QD or BID resulted in 
a mean skin flux of INCB018424 ranging from 54 ± 41 ng/cm2/h (Cohort A) through 422 ± 200 
ng/cm2/h (Cohort C). The mean skin flux of INCB018424 increased with increasing application 
strength. The mean systemic bioavailability was 2.8 ± 3.2%, 3.0 ± 1.9%, 3.0 ± 1.9%, 2.7 ± 1.1%, 
and 2.7 ± 2.3% for Cohorts A through E, respectively. The systemic bioavailability of 
INCB018424 applied as a topical cream appears independent of the strength of the cream 
formulation. 
 
Study INCB 18424-202: In the topical subtotal inunction study in 25 subjects with psoriasis, there 
were no subjects who discontinued from the study due to an AE and there were no deaths reported 
during the study. Overall, 4 TEAEs were considered at least possibly related to the study drug. 
These included transient leukopenia (unconfirmed on repeat testing), reticulocytosis, transient 
hypoesthesia, and transient application site irritation [23].  
The average plasma concentrations of INCB018424 for Cohort A , Cohort B, Cohort C, Cohort 
D, and Cohort E were 7.00 ± 2.11 nM, 29.38 ± 13.10 nM, 24.42 ± 10.07 nM, 34.96 ± 20.43 nM, 
and 60.99 ± 73.85 nM, respectively, at the steady state. The mean INCB018424 Css increased 
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approximately proportional to application dose per day. The mean skin flux of INCB018424 
was estimated to be 180 ± 126 ng/cm2/h, 131 ± 92 ng/cm2/h, 60 ± 43 ng/cm2/h, 151 ± 126 
ng/cm2/h, and 152 ± 74 ng/cm2/h, respectively, for Cohorts A, B, C, D, and E. The mean topical 
bioavailability was estimated to be 3.8 ± 2.5%, 4.1 ± 3.4%, 3.4 ± 1.9%, 3.9 ± 1.3%, and 5.2 ± 
1.9%, respectively, for Cohorts A, B, C, D, and E. Based on this result, it is concluded that the 
systemic bioavailability of INCB018424 applied as a topical cream is independent of the 
strength of the cream formulation and BSA. 
 
Study INCB18424-203: In the double-blind, vehicle-controlled study in 199 subjects with psoriasis, 
30 subjects (15.1%) across treatment groups experienced treatment-related TEAEs. Overall, these 
events were mild or moderate in intensity and generally resolved with or without the need for 
concomitant medication; 6 events that were possibly related to treatment resulted in subject 
discontinuation from the study. Across groups, 15 subjects (7.5%) discontinued from the study due 
to AEs and 17 subjects (8.5%) discontinued study drug application due to AEs. Four subjects (2 
subjects each in the INCB018424 1.0% and 1.5% treatment groups) had their study drug temporarily 
withdrawn, and 1 subject in the INCB018424 1.5% treatment group had their study drug dosage 
reduced due to application site papules (unrelated to treatment). The most frequent AEs were 
nasopharyngitis, upper respiratory tract infection, application site irritation, and application site 
pruritus. There were no deaths reported during the study. Nine subjects reported 12 serious, severe, 
and/or life-threatening TEAEs, of which only 1 was considered related, a Grade 3 event of GGT 
increased in a 51-year-old woman. Three subjects discontinued study participation because of 
serious, severe, and/or life-threatening TEAEs. Since all but one of the serious, severe, and/or life-
threatening AEs were not related to treatment, the cumulative events are considered to not 
contribute to the overall risk assessment[23].  
 
Application of INCB018424 0.5%, 1.0%, and 1.5% cream QD resulted in a Css,min of 
INCB018424 of 9.19 ± 11.77 nM, 16.99 ± 19.05 nM, and 19.97 ± 25.13 nM, respectively, for 
0.5% QD to 1.5% QD. Thus, the mean INCB018424 Css,min increased approximately 
proportional to application dose. As the severity of lesion thickness, erythema, and scale 
increased, the INCB018424 Css,min appeared to be decreased for the same treatment. The 
subjects with less severe lesion thickness, erythema, and scale seemed to have higher trough 
INCB018424 exposures. 
 
Study INCB 18424-204: This was a 2-part, open-label and double-blind, vehicle-controlled study in 
90 subjects with AA. In Part A through Week 24, 9 subjects (75.0%) had a TEAE. One subject had 
Grade 3 SAEs of noncardiac chest pain, infected neoplasm, and sepsis, all judged not related to 
study drug by the investigator, that led to interruption of study drug; these events resolved, and the 
subject resumed study drug. All of the TEAEs in Part A occurred in 1 subject each. The majority of 
TEAEs were mild or moderate. In the open-label extension for Part A, 7 subjects (77.8%) had a 
TEAE. One subject had an SAE of lentigo maligna judged not related to study drug by the 
investigator; the lesion was excised and no action was taken with study drug. The most frequently 
reported TEAE during the open-label extension of Part A was back pain (2 subjects [22.2%]); all 
other TEAEs occurred in 1 subject each. The majority of TEAEs were mild or moderate.  In Part B 
through Week 24, 23 subjects (59.0%) in the INCB018424 cream group and 27 subjects (71.1%) in 
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the vehicle group had a TEAE. The most frequently reported TEAE in subjects receiving 
INCB018424 cream was nasopharyngitis (6 subjects, 15.4% compared with 5 subjects [13.2%] in 
the vehicle group). The only other TEAEs reported in more than 1 subject receiving INCB018424 
cream included pruritus (5 subjects, 12.8% in the INCB018424 group and 3 subjects [7.9%] in the 
vehicle group), headache (3 subjects, 7.7% in the INCB018424 group and 0 subjects in the vehicle 
group), and skin exfoliation (2 subjects, 5.1% in the INCB018424 group and 3 subjects, 7.9% in the 
vehicle group). One subject had an SAE of generalized anxiety disorder that was judged not related 
by the investigator and led to interruption of study drug. In Part B through the data cutoff, of the 63 
subjects treated with open-label INCB018424 cream, 10 subjects (32.3%) randomized to 
INCB018424 and 22 subjects (68.8%) randomized to vehicle had a TEAE. The most frequent TEAE 
reported was nasopharyngitis, which was reported in 5 subjects (16.1%) randomized to INCB018424 
cream and 2 subjects (6.3%) randomized to vehicle. One subject in Part B had an SAE of 
diverticulitis during open-label treatment that was judged by the investigator as not related to study 
drug; the subject remained on study drug during this event [23]. 
Twelve subjects were enrolled in Part A (INCB018424 1.5% cream BID). Similar mean plasma 
concentrations were observed between trough and Css in Part A. 
 
Higher trough plasma concentrations were observed in Part A compared with Part B. Similar 
mean trough concentrations were observed between Weeks 12 and 24 for both strata in Part B. 
Trough concentrations for subjects with 50% to 100% of scalp involvement with AA at baseline 
was almost double of that for subjects 25% to < 50% of scalp involvement with AA at baseline in 
Part B. 
 
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Study INCB 18424-206: This was a double-blind, active- and vehicle-controlled study in adults with 
AD. One hundred forty-seven subjects were randomized, and 132 subjects were treated with blinded 
study drug as of the cutoff date (28 JUN 2017). Blinded, unaudited data showed that 23 of the 132 
treated subjects (17.4%) had a TEAE. The most frequently reported TEAE was nasopharyngitis, 
which occurred in 3 subjects (2.3%). One SAE of myocardial infarction was reported but was 
assessed by the investigator as not related to study drug; the subject had elevated cholesterol at 
baseline and was a long-time smoker, which likely contributed to the event. Of the 35 subjects who 
entered the open-label extension, 6 subjects (17.1%) had a TEAE. All TEAEs reported in the open-
label extension occurred in 1 subject each. No SAEs occurred during the open-label extension[23]. 
No PK data were available as of the data cutoff date. 
Topical ruxolitinib cream’s limited adverse cutaneous events has been supported by clinical trials to 
date where cutaneous AEs have been infrequent and of similar frequency and severity as with 
vehicle control treatment. Adverse events reported with topical ruxolitinib were mostly related to 
application site, mostly mild to moderate (and judged to be unrelated to study medication), resolved, 
and did not require treatment discontinuation. Cutaneous AEs (dryness, pruritus, eczema, skin 
peeling) were seen with similar frequency in vehicle and topical ruxolitinib cream groups. Laboratory 
and ECG evaluations have not suggested any safety issues, specifically no instances of 
neutropenia, thrombocytopenia, or leukopenia. Based on vehicle controlled studies with topical 
ruxolitinib 1.5% cream, we do not expect significant systemic toxicities or local side effects from 
treatment with topical ruxolitinib 1.5% cream[23].  
All toxicities will be graded as per the Common Terminology Criteria for Adverse Events (CTCAE) 
version 5.0, and as applicable. All AEs (or clinically severe cutaneous adverse events, when CTCAE 
v5.0 grading not applicable) grade ≥2 with  any attribution will be reported from initial application of 
topical intervention through the 56 day (and in those patients with a day 84) follow-up visit, and will 
be followed until the event resolves. If the AE does not stabilize/ resolve within a reasonable time 
(approximately 30 days), it should be followed until its clinical relevance and etiology can be 
reasonably explained[23]. 
Less common expected application-side adverse events include[23]: 
 
Dry skin 
 
Erythema 
 
Skin peeling 
 
Application site reactions irritation 
 
Skin burning 
 
Application site pruritus 
General adverse events (unlikely or possibly to be related to topical ruxolitinib 1.5% cream), in both 
topical ruxolitinib 1.5% cream and vehicle arms of clinical trials include (in order of frequency)[23]: 
 
Upper respiratory tract infection 
 
Nasopharyngitis 
 
Sinusitis 
 
Influenza 
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 
Back pain 
 
Electrocardiogram QT interval abnormal 
 
Diarrhea 
 
Gastroenteritis 
 
Headache 
 
Seasonal allergy 
 
Transient leukopenia 
 
Reticulocytosis 
 
Transient hypoesthesia 
Based on a review of the extent of exposure, the incidence of AEs (including nonserious events, 
serious, severe, and/or life-threatening events, treatment-related events, and events that led to 
subject discontinuation), the clinical laboratory outcomes, the vital sign measurements, and the 
ECG findings, no safety signals or trends were observed.  
All serious adverse events will be reported from initial application of study interventions through the 
day 56 ± 5 days safety visit, and the day 84 ± 5 days safety visit for those who repeat a topical 
ruxolitinib course, and will be followed until resolution. 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
The primary outcome of this study is the difference in body surface area (BSA) (Appendix I-II) of 
non-sclerotic and superficially sclerotic cutaneous cGVHD between ruxolitinib treated side and 
vehicle treated sides of the face/body at study completion (day 28 ± 3 days). Clinical assessment at 
all study visits, including baseline BSA will be performed by a dermatologist (Dr. Alina Markova,Dr. 
Mario E. Lacouture, Dr Veronica Rotemberg, or Dr. Sarah Noor).  , and subsequently BSA will be 
calculated via photos by a single bone marrow transplantation hematologist.  
 
Criteria for evaluation of clinical efficacy 
No validated instruments for clinical assessment of chronic cutaneous GVHD exist[24]; we propose 
to use efficacy criteria that have been previously developed for evaluation of cutaneous T-cell 
lymphoma[25]. The body surface area (BSA) is the primary endpoint of efficacy. Secondary 
endpoints of efficacy include: Physician’s Global Assessment of Clinical Condition (PGA), or the 
Composite Assessment of Index Lesion Severity (CAILS) grading scales are the  secondary end 
points of efficacy[25]. The PGA will be the investigators’ subjective assessment of the overall 
improvement or worsening in disease compared with the baseline assessment[25].  
 
The CAILS assessment will generate a separate composite score for the treated and non-treated 
sides of the study participant. The assessment data to generate the composite score will be 
generated from case report form from the study visit. The treatment and vehicle sides of the body 
will be assessed for erythema, scaling, pruritus and size. For erythema, scaling and pruritus, the 
following grading system will be used.  
 
CAILS Grading Tool for Erythema, Scaling, Pruritus  [25] 
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Scale 
Grade 
0 
No evidence of sign or symptom 
1 
Intermediate interval 
2 
Mild: less than average presentation of sign or symptom 
3 
Intermediate interval 
4 
Moderate: average disease presentation of sign or symptom 
5 
Intermediate interval 
6 
Severe: >25% worse than average severity of sign or symptom 
7 
Intermediate interval 
8 
Very severe: the near worst severity of sign or symptom 
*Intermediate intervals 1, 3, 5, and 7 serve as midpoints between the defined grades of 0, 2, 4, 6 
and 8. 
 
An estimate for the % involvement of the right and left areas will be assessed on scale of 0 to 11 as 
follows:  
CAILS Grading Tool for BSA Involvement 
Grade 
BSA within marked treatment
 area on each side  
0 
0 
1 
>0 and ≤2 
2 
>2 and ≤4 
3 
>4 and ≤6 
4 
>6 and ≤8 
5 
>8 and ≤10 
6 
>10 and ≤12 
7 
>12 and ≤14 
8 
>14 and ≤16 
9 
>16 and ≤18 
10 
>18 and <20 
11 
20 
 
Composite Assessment of Index Lesion Disease Severity (CAILS): Signs and Symptoms and 
BSA Grade for Each of the 2 Selected Sides[25] (Extracted by unblinded Research Study 
Assistant from Physician-completed Appendix V) 
Clinical Sign and Size 
Non-Treated Area 
          Treated Area 
Erythema 
a (range 0-8) 
e (range 0-8) 
Scaling 
b (range 0-8) 
f (range 0-8) 
Pruritus 
c (range 0-8) 
g (range 0-8) 
Size (BSA) 
d (range 0-11) 
h (range 0-11) 
 
 
 
Total  
a+b+c+d (range 0-35) 
e+f+g+h (range 0-35) 
 
 
Separate summary scores for the treated and non-treated sides of the face/body will be created by 
summing ∑(a-d) and ∑(e-h), respectively. We will calculate a ratio of the day 28 assessment total 
score to baseline assessment total score for the treated and non-treated sides of the participant. We 
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will evaluate the difference in the ratios between the treated and non-treated sides of the face/body 
for each study participant.   
 
Physician’s Global Assessment of Clinical Condition (PGA)[25] 
Grade 
Description 
Response 
0 
Completely clear: no evidence of disease (100% improvement) 
Clinical 
Complete 
Response 
1 
Almost clear: very significant clearance (>90% to <100%); only traces of 
disease remains 
Partial 
Response 
2 
Marked improvement: significant improvement (≥75% to <90%); some 
evidence of disease remains 
3 
Moderate improvement: intermediate between slight and marked 
improvement (≥50% to <75%) 
4 
Slight improvement: some improvement (≥25% to <50%); however, 
significant evidence of disease remains 
Stable 
Disease 
5 
No change: disease has no changed from baseline condition (±<25%) 
6 
Worse: disease is worse than at baseline evaluation by ≥25% or more 
Progressive 
Disease 
 
All patients who complete the day 28 +/- 3 days study visit will be eligible for the primary outcome of 
the study. The primary outcome of this study is the difference in body surface area (BSA) of non-
sclerotic and superficially sclerotic cutaneous cGVHD between ruxolitinib treated side and vehicle 
treated sides of the face/body at study completion (day 28 visit). Assessment for BSA involvement, 
PGA, and CAILS will be made by a single dermatologist during the patient encounter. The 
dermatologist will record an estimate of involved BSA, PGA, and CAILS for both sides of the body in 
a blinded fashion. The CAILS score will be subsequently calculated by research study assistant 
(RSA), as described above, and the dermatologist and hematologist will be blinded to that score. In 
addition, clinical images will be taken of the treatment and placebo sides of the body at each patient 
visit to additionally document BSA involvement. The clinical evaluation, by the dermatologist, will be 
used for the efficacy assessment.  
The secondary outcomes of this study are: (1) The difference in the Physician’s Global Assessment 
of Clinical Condition (PGA) of non-sclerotic and superficially sclerotic cutaneous cGVHD between 
ruxolitinib treated side and vehicle treated sides of the face/body at study completion (day 28 visit); 
(2) The difference between the ratios of the day 28 CAILS total score to baseline CAILS total score 
of non-sclerotic and superficially sclerotic cutaneous cGVHD between ruxolitinib treated side and 
vehicle treated sides of the face/body at study completion; (3) Difference in the body surface area 
(BSA), Physician’s Global Assessment of Clinical Condition (PGA), and the objective Composite 
Assessment of Index Lesion Severity (CAILS) of non-sclerotic and superficially sclerotic cutaneous 
cGVHD between ruxolitinib treated side and vehicle treated sides of the face/body at study 
completion (day 14 visit); (4) The difference in patient-reported outcomes between the side of the 
face and body treated with topical ruxolitinib cream versus the contralateral side treated with twice 
daily vehicle at day 14 visit and day 28 visit using the adapted National Cancer Institute Patient-
Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-
CTCAE™) questionnaire; (5) The difference in chronic cutaneous non-sclerotic and superficially 
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sclerotic GVHD BSA between the sides of the face/body treated with topical ruxolitinib and vehicle 
by measuring the agreement of blinded independent physician’s review of standardized photography 
of the right and left sides of the face and body respectively performed at day 28 visit; (6) The safety 
and tolerability of topical ruxolitinib by physical examination and adverse event reporting; (7) 
Accrual, retainment and compliance with therapy 
 
13.0 
CRITERIA FOR REMOVAL FROM STUDY 
Patients will be removed from the study (and will not be replaced) if: 
 
They develop an adverse event necessitating discontinuation of topical interventions. 
 
They require greater than 14 days off therapy due to a treatment-related adverse event. 
Patients will be removed from the study and replaced if: 
 
They enroll in an alternate systemic clinical trial which prohibits concurrent topical clinical trial 
participation.  
 
They choose to withdraw consent for continued participation. 
 
Death occurs. 
All patients who receive ruxolitinib and report using the treatment will be evaluable for toxicity.  
14.0 
BIOSTATISTICS 
Target sample size is 24 patients, wherein 12 patients will be randomized to topical ruxolitinib to 
right side and 12 patients to the left side, with placebo cream on contralateral side. For each side of 
the face/body, non-sclerotic and superficially sclerotic chronic cutaneous GVHD BSA, PGA, and 
CAILS will be assessed in real-time by the study dermatologist observer blinded to the treatment 
status. The methodology for the real-time BSA calculation is available in Appendix I,II. The efficacy 
endpoint for the primary objective will be the difference in body surface area (BSA) as recorded by 
the dermatologist of non-sclerotic and superficially sclerotic cutaneous cGVHD between the topical 
ruxolitinib and vehicle treated sides of the face/body at study day 28. In this pilot study, we are 
utilizing three different measures to assess efficacy to qualitatively evaluate which works best for the 
clinician within the context of the patient visit. The bone marrow transplantation oncologist will 
subsequently calculate the BSA via total body photographs taken during the visit. Maximum BSA for 
topical ruxolitinib application will be 20% of overall BSA. All BSA, PGA, and CAILS assessments 
performed at study days 14± 3 days and study day 28 ± 3 days will be performed by the study 
dermatologist in real-time and serve as the data for the efficacy analysis. All BSA will also be 
calculated virtually by one bone marrow transplantation hematologist in review of total body 
photographs performed during visit, blinded to treatment, but will not contribute to efficacy 
assessments. Participants will only be included in the primary endpoint analysis if they complete the 
28 ± 3 days assessment. Descriptive statistics and graphical methods will be employed to evaluate 
participant characteristics and the distribution BSA, PGA, and CAILS differences at each evaluation 
time point. Paired t-tests will be performed to assess differences in BSA. In addition, since the 
overall area treated may vary slightly between participants, we will use linear regression with the 
difference between treatment and control areas at day 28 as the dependent variable, and the total 
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treatment area BSA as the independent variable. Regresion coefficients along with 95% 
confidence intervals will be reported for this treatment area adjusted difference.  
The primary aim is to assess the efficacy of ruxolitinib 1.5% cream for the treatment of non-sclerotic 
and superficially sclerotic chronic cutaneous GVHD at day 28 visit. This is a pilot study. With the 
average body surface area for male and female adult cancer patients has been estimated to be 
1.9m2 and 1.7m2, respectively[26].Using an average BSA of 1.8m2 (18,000 cm2) for our mixed 
sample; if we and treat, on average, 5.0% BSA per participant, we expect to have equivalent areas 
of 0.09m2 or 900cm2 of treatment and control areas per participant. 
Table. Effect size calculations for the minimum detectable difference in area between treatment and 
control sides of the participant based on varying levels of correlation between treatment and control 
areas within participant.  
Effect 
Size 
Difference in area 
between 
treatment and 
control areas (cm2) 
Control 
area 
(cm2) 
Treatment 
area (cm2) 
SD of the 
difference 
SD 
Control 
area 
Correlation 
between 
treatment and 
control areas 
 
-0.5972 
-400.6 
900 
499.4 
670.8 
500 
0.1 
-0.5972 
-377.7 
900 
522.3 
632.5 
500 
0.2 
-0.5972 
-353.3 
900 
546.7 
591.6 
500 
0.3 
-0.5972 
-327.1 
900 
572.9 
547.7 
500 
0.4 
-0.5972 
-298.6 
900 
601.4 
500 
500 
0.5 
-0.5972 
-267.1 
900 
632.9 
447.2 
500 
0.6 
-0.5972 
-231.3 
900 
668.7 
387.3 
500 
0.7 
-0.5972 
-188.8 
900 
711.2 
316.2 
500 
0.8 
 
So, based on these estimates, if we select lesional areas on a patient equivalent to 5% BSA (which 
is roughly 900cm2 for both treatment and control sides), and we have an estimated common 
standard deviation of 500, with 80% power, a two-sided test, an alpha level of 5%, and a correlation 
between treatment and control areas of 0.4, we can expect to detect a 327.1cm2 difference between 
treatment and control areas at the day 28 evaluation. The effect size calculation is based on a paired 
t-test. Since we do not have any pilot data for these calculations, the estimate for the standard 
deviation that utilized for these estimates comes from experience with conditions with a similar 
presentation. The Table above lists the expected differences between treatment and control areas 
based on a range of correlations.  
Secondary endpoints include: 
1. Physician’s Global Assessment of Clinical Condition (PGA) at day 28 
The difference in the PGA score of non-sclerotic and superficially sclerotic cutaneous 
cGVHD between the topical ruxolitinib and vehicle treated sides of the face/body will be 
calculated. The Wilcoxon signed rank test will be used to assess differences in these paired 
assessments for the day 28 assessment.   
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2. Composite Assessment of Index Lesion Severity (CAILS) 
The difference between the ratios of the day 28 CAILS score to baseline CAILS score of non-
sclerotic and superficially sclerotic cutaneous cGVHD between ruxolitinib treated side and 
vehicle treated sides of the face/body at study completion.We will use descriptive statistics to 
describe the distribution of the difference in CAILS ratios between treated and vehicle sides 
of the body. The difference in ratios will be assessed using a paired t-test. 
3. Efficacy at day 14  
Little is known about the efficacy of this treatment in this patient population. As a secondary 
aim, we will assess efficacy at the 14 day visit as we described for the primary aim of the 
study using paired t-tests and linear regression to control for potential differences in overall 
treatment areas between study participants.  
4. Patient-reported Outcomes 
Patient reported outcomes measured by the NCI Patient Reported Outcomes-Common 
Terminology Criteria for Adverse Events (PRO-CTCAE™) for each side of face/body affected 
by GVHD rash; a Likert-scale patient-reported assessment of change in the treated areas 
has been appended to adapt the PRO-CTCAE™ for this study. PRO-CTCAE™ instrument 
will be scored as ascribed by methods published for this instrument. Overall summary 
measures and subdomain measures will be summarized using descriptive statistics. To 
evaluate differences in the paired responses, for the overall PRO-CTCAE score and for each 
of the subdomain scores, the Wilcoxon signed rank test will be used.   
5. Agreement between GVHD BSA Measurements 
GVHD BSA measurements will be evaluated during the patient visit by a dermatologist, and 
by an additional bone marrow transplant physician using digital clinical images captured 
during the patient visit. The GVHD BSA assessments for both evaluations will be visually 
assessed using scatterplots of the two independent assessments and compared using Lin’s 
concordance correlation coefficient.  
 
6. Safety and Tolerability  
All patients will be evaluable for adverse events (toxicities) from the time of their first 
treatment with ruxolitinib until the end of the study visits or until they are lost to follow-up.  
All reported adverse events (AEs grade ≥2 with any attribution) during the study period 
through day 56 follow-up  [,and day 84 ± 5 days for subjects who continue in the open-label 
extension] visit will be coded using Medical dictionary for regulatory activities (MedDRA) 
Version 20.0. For all adverse events, all treatment-emergent adverse events, all serious 
adverse events, and all adverse leading to discontinuation frequency distributions by system 
organ class and preferred term will be calculated and presented for each patient and each 
treatment side, when applicable. The safety of all patients enrolled in this study will be 
monitored throughout the study, and at safety visit 28 ± 5 days following the last study dose. 
Safety monitoring will include history and physical examination with adverse event reporting. 
A follow-up safety evaluation will be done until end of study visit after discontinuing topical 
ruxolitinib cream treatment or withdrawal from the study for any reason. In addition, patients 
should notify the study staff of any problems that occur between visits by telephone and, if 
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necessary, be evaluated by the Investigator or study staff at an unscheduled interim hospital 
visit. 
Treatment adjustments:Patients who report or exhibit treatment-related AEs should have 
their treatment exposure reduced or discontinued. If no frequency of study drug application is 
tolerated for any of the patient’s lesional skin, then the patient must be withdrawn from the 
study. Treatment interruptions for non-medical reasons are at times unavoidable and are 
permissible under this protocol but must be documented. However, every attempt should be 
made to avoid any non-medical treatment delays 
 
Grade 1 – 2: No change to study drug dose. Continue clinical monitoring. 
 
Grade 3 (with attribution possibly, probably, or definitely related): Hold study drug 
until AE improves to grade ≤2. 
 
Grade 4 (with attribution possibly, probably, or definitely related): Discontinue study 
drug. 
Adverse Event Definitions  
The following definitions of terms guided by the International Conference on Harmonization 
and the US Code of Federal Regulations apply to this section:  
An adverse event (AE) is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product that does not necessarily have a 
causal relationship with this treatment.  
Serious adverse event (SAE) is any adverse event that is fatal or life-threatening, is 
permanently disabling, requires or prolongs inpatient hospitalization, or is a congenital 
anomaly, or any important medical event.  
 
Life-threatening, for the purpose of reporting adverse events, refers to an event in 
which the patient was, in the view of the initial reporter, at immediate risk of death at 
the time of the event as it occurred (i.e., it does not refer to an event which might 
have resulted in death if it were more severe).  
 
Hospitalization describes a period of at least 24 hours. Over-night stay for 
observation, stay at emergency room or treatment on an out-patient basis do not 
constitute a hospitalization. However, medical judgment must always be exercised 
and when in doubt the case should be considered serious (i.e. if case fulfills the 
criterion fora medically important event).  
o Hospitalizations for administrative or social purposes do not constitute a 
serious adverse event.  
o Hospital admissions and/or surgical operations planned before trial inclusion 
are not considered AEs, if the illness or disease existed before the subject 
was enrolled in the trial, provided that the condition did not deteriorate during 
the trial. Associated with the use of the drug means that there is a reasonable 
possibility that the event may have been caused by the drug. 
  
Toxicity information will be presented on an individual basis and will be summarized using 
descriptive statistics.  
7. Accrual, retainment and compliance with therapy  
Since this study involves a novel patient population for our department, we will evaluate 
metrics on the number of patient accrued relative to the number approached. We will also 
assess retainment at each study time point. Compliance with application of the study 
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medications will be assessed via patient logs. 
 
Descriptive statistics will be provided for patient characteristics, efficacy, patient-reported 
outcomes, safety and tolerability, and minimally invasive skin tape strip molecular profiles as 
appropriate. Patients will be evaluable for the efficacy assessment if they complete the 28 
day (+/-3 day) assessment. If patients miss other planned assessments, they will still be 
evaluable for the primary objective. 
We expect to accrue 1 – 4 patients per month, and expect to complete enrollment in 6-26 
months.  
15.0 
 RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
15.1 
Research Participant Registration 
Confirm eligibility as defined in the section entitled Inclusion/Exclusion Criteria. Obtain 
informed consent, by following procedures defined in section entitled Informed Consent 
Procedures. During the registration process registering individuals will be required to 
complete a protocol specific Eligibility Checklist. The individual signing the Eligibility Checklist 
is confirming whether or not the participant is eligible to enroll in the study. Study staff are 
responsible for ensuring that all institutional requirements necessary to enroll a participant to 
the study have been completed. See related Clinical Research Policy and Procedure #401 
(Protocol Participant Registration). 
 
15.2 
Randomization 
This is a double blind randomized comparison of topical ruxolitinib to topical vehicle: Topical 
ruxolitinib 1.5% cream on left or right side of face/body vs. vehicle on contralateral side of 
face/body. Patients will be randomized to determine which side of the face/body (i.e., right or 
left) will be treated with topical ruxolitinib 1.5% cream, and the contralateral side will be 
treated with the control vehicle. Randomizing the treatment side is to maintain blinding of the 
physician. For example: if patients are all assigned to apply topical ruxolintib to their right 
side and are showing clinical improvement on each patient’s right side consistently, the 
physician will be aware that the right side is the treated side, possibly adding bias to the 
study. Variability in application side will also help to account for inter-patient variability in 
application with right- versus- left hand. After eligibility is established and immediately after 
consent is obtained, patients will be registered in the Clinical Trail Management System 
(CTMS). After registration, patients will be randomized in the Clinical Research Database 
(CRDB). Randomization will be accomplished by the method of random permuted block. 
Since this is a double-blinded study, the patients’ treatment assignments can be viewed in 
the CRDB only by the hospital pharmacists who are dispensing the study drugs.   
At the end of the 28 ± 3 days study visit, patients will remain blinded to treatment arms.After 
trial completion (day 28 ± 3 days), all patients will be offered repeated treatment cycle with 
topical ruxolitinib or standard of care therapy .  
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 32 of 38 
The PI will contact DMR to obtain patients’ treatment assignments at trial conclusion for data 
analysis. 
16.0 
DATA MANAGEMENT ISSUES 
Data forms will be developed for recording all information pertinent to the observations and 
tests described in this protocol. All study data will be collected by an assigned data manager 
who will enter this information into MSK Medidata in a timely and accurate manner. All data 
and forms gathered for this study will be collected and stored in a secure location in facilities 
of the Dermatology Service. Regular meetings attended by the data manager and the 
Principal Investigators will be held to review study progress and to manage any difficulties 
encountered.  
 
The data manager will collect toxicity and self-reported compliance data via patient’s diaries 
and patient interviews. Adverse events, including all toxic effects related to treatment will be 
recorded individually according to toxicity date.  
 
All clinical photographs will be maintained in digital format in a computerized archive 
(DermagraphixTM). This system labels each clinical photograph with study subject MRN, 
lesion number, and photograph date. 
 
All patient data and questionnaires will be accessed on the Health Information System (HIS) 
and Mirror Dermagraphix database, which are password protected with user level access. All 
the data will be entered and maintained in MSK Medidata.During data analysis, de-identified 
data will be sent to investigators at Hackensack Medical Center for collaboration and 
manuscript preparation. All de-identified shared with Hackensack Medical Center invstigators 
will be sent via MSK secure email.  
 
The first interim data analysis will occur after the study has accrued 10 evaluable 
participants. Only the biostatician and Dermtech personnel will be unblinded during the 
analysis.  
 
The second interim data analysis will occur with the remaining 14 evaluable participants. 
Only the biostatician and Dermtech personnel will be unblinded during the analysis. 
 
Estimated time of accrual: 26 months 
Accrual Rate: 1-4 patients per month 
Time to complete study: 36 months 
 
16.1 
Quality Assurance 
Study personnel will generate monthly registration reports to monitor patient accrual and 
completeness of registration data. Routine data quality reports will be generated to access 
missing data and inconsistencies. Accrual rates, extent and accuracy of evaluations and 
follow-up will be monitored periodically throughout the study period and potential problems 
will be brought to the attention of the study team for discussion and action. 
 
Data quality and protocol compliance audits will be conducted by the study team on a regular 
basis throughout the study period 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 33 of 38 
16.2 
Data and Safety Monitoring 
Data and safety monitoring audits will be conducted by the study team on a regular basis 
throughout the study period. The Data and Safety Monitoring (DSM) Plans at Memorial 
Sloan-Kettering Cancer Center were approved by the National Cancer Institute in September 
2001.  The plans address the new policies set forth by the NCI in the document entitled 
“Policy of the National Cancer Institute for Data and Safety Monitoring of Clinical Trials” 
which can be found at:  http://cancertrials.nci.nih.gov/researchers/dsm/index.html. The DSM 
Plans at MSKCC were established and are monitored by the Office of Clinical Research.  
The MSKCC Data and Safety Monitoring Plans can be found on the MSKCC Intranet at: 
http://mskweb2.mskcc.org/irb/index.htm 
 
There are several different mechanisms by which clinical trials are monitored for data, safety 
and quality.  There are institutional processes in place for quality assurance (e.g., protocol 
monitoring, compliance and data verification audits, therapeutic response, and staff 
education on clinical research QA) and departmental procedures for quality control, plus 
there are two institutional committees that are responsible for monitoring the activities of our 
clinical trials programs.  The committees: Data and Safety Monitoring Committee (DSMC) for 
Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase III 
clinical trials, report to the Center’s Research Council and Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required.  Every type of protocol (e.g., NIH sponsored, 
in-house sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed 
and the monitoring procedures will be established at the time of protocol activation.  
 
17.0 
PROTECTION OF HUMAN SUBJECTS 
Prior to the enrollment of each patient, the risks, benefits and objectives of the study will be reviewed 
with the participant, including a discussion of the possible side effects. Patients reserve the right to 
withdraw participation from this study at any time.   
 
Risks: It’s unlikely that significant risks will be associated with the limited use of topical ruxolitinib 
1.5% cream planned in this study. 
 
Benefits: The early use of topical ruxolitinib 1.5% cream is hypothesized to reduce BSA of non-
sclerotic and superficially sclerotic chronic cutaneous. This would serve as a novel topical therapy 
for management of non-sclerotic and superficially sclerotic chronic cutaneous GVHD and would 
improve patients’ symptoms during treatment. 
 
Possible toxicities/ adverse events. Local application-site side effects anticipated with ruxolitinib 
include dry skin, erythema, pruritus, skin peeling, and irritation. These adverse effects are not 
expected to necessitate treatment interruption. Systemic toxicities are rare, including upper 
respiratory tract infection and nasopharyngitis. Toxicities of topical ruxolitinib 1.5% cream are 
elaborated in section 11.0 of this protocol. The investigators will use a standardized form to assess 
irritation, pruritus, erythema and during the visits, as well as rare reactions that could be reported by 
the patient. 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 34 of 38 
 
Consent process: Participation in this protocol is voluntary. All patients will be required to sign a 
statement of informed consent, which must conform to MSKCC IRB guidelines. 
 
Costs: Patients will not be charged for protocol related costs 
 
Alternatives: There are no FDA-approved topical therapies for the treatment of non-sclerotic or 
superficially sclerotic chronic cutaneous GVHD; however, efficacy has been reported with topical 
corticosteroids.  
 
Confidentiality: Every effort will be made to maintain patient confidentiality. Research and hospital 
records are confidential. Patients’ names and any other identifying information will not be used in 
reports or publications resulting from this study. Other authorized agencies and appropriate 
personnel may review patient records as required. 
 
17.1 
Privacy 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB).  
The consent indicates that individualized de identified information collected for the purposes 
of this study may be shared with other qualified researchers. Only researchers who have 
received approval from MSK will be allowed to access this information which will not include 
protected health information, such as the participant’s name, except for dates. It is also 
stated in the Research Authorization that their research data may be shared with other 
qualified researchers. 
17.2 
Serious Adverse Event (SAE) Reporting 
An adverse event is considered serious if it results in ANY of the following outcomes: 
 
Death 
 
A life-threatening adverse event 
 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
 
A congenital anomaly/birth defect 
 
Important Medical Events (IME) that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon medical judgment, they may 
jeopardize the patient or participant and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition 
Note: Hospital admission for a planned procedure/disease treatment is not considered an SAE. 
 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 35 of 38 
SAE reporting is required as soon as the participant starts investigational treatment/intervention. 
SAE reporting is required for 30-days after the participant’s last investigational 
treatment/intervention. Any event that occur after the 30-day period that is unexpected and at least 
possibly related to protocol treatment must be reported. 
 
Please note: Any SAE that occurs prior to the start of investigational treatment/intervention and is 
related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per IRB 
SOP RR-408 ‘Reporting of Serious Adverse Events’, the SAE report must be submitted within 5 
calendar days of the event. All other SAEs must be submitted within 30 calendar days of the event. 
 
The report should contain the following information: 
 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o An explanation of how the AE was handled 
o A description of the participant’s condition 
o Indication if the participant remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
For IND/IDE protocols: The SAE report should be completed as per above instructions. If 
appropriate, the report will be forwarded to the FDA by the IND Office 
 
 
17.2.1  
SAE Reporting to Incyte 
Incyte needs to be notified within 24 hrs of learning of an event. Incyte also needs to be 
provided a completed SAE form via email. 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. Any SAEs occurring 
more than 30 days after the last dose of protocol treatment should be reported only if the 
investigator suspects a causal relationship to the protocol treatment. 
Initial Serious Adverse events (SAEs) and/or subsequent follow-up reports will be reported 
via email to: SafetyReporting@Incyte.com, fax (+) 1-866-981-2057.  SAE reports will be for a 
single subject. 
SAE forms will be emailed with a cover sheet to the IST email address: 
SafetyReporting@Incyte.com, fax (+) 1-866-981-2057. 
Reporting of Pregnancy to Incyte 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 36 of 38 
An “Initial Pregnancy Report” or equivalent will be completed in full and emailed to 
SafetyReporting@Incyte.com, fax (+) 1-866-981-2057 within 24 hrs of discovery of a 
pregnancy of a subject who has taken ruxolitinib.  The “Follow-up Pregnancy Report Form” 
or equivalent must be completed and emailed to SafetyReporting@Incyte.com, fax (+) 1-866-
981-2057 within 30 days after delivery, so that Incyte is provided with information regarding 
the outcome of the pregnancy.   
Data on fetal outcome and breastfeeding are collected for regulatory reporting and drug 
safety evaluation. Follow-up should be conducted for each pregnancy to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications, by following until the first well-baby visit. Pregnancy should be recorded on a 
Pregnancy form and reported by the investigator. Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal 
relationship to the sponsor's study drug to any pregnancy outcome, as well as follow-up to 
the first well-baby visit or the duration specified in local regulations, whichever is later. If the 
pregnancy results in any events which meet the serious criteria (i.e., miscarriage or 
termination), the SAE reporting process will be followed and the timelines associated with an 
SAE will be followed. 
18.0 
INFORMED CONSENT PROCEDURES 
Before protocol-specified procedures are carried out, consenting professionals will explain 
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following:  
1. The nature and objectives, potential risks and benefits of the intended study.  
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time.  
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 37 of 38 
 
19.0 
REFERENCES 
1. 
Lee, S.J. Track 2 (Experienced): Chronic Graft-versus-Host Disease. in Clinical Research 
Professionals / Data Management. 2010. www.cibmtr.org. 
2. 
Cooke, K.R., et al., The Biology of Chronic Graft-versus-Host Disease: A Task Force Report 
from the National Institutes of Health Consensus Development Project on Criteria for Clinical 
Trials in Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant, 2017. 23(2): p. 
211-234. 
3. 
Arai, S., et al., Increasing incidence of chronic graft-versus-host disease in allogeneic 
transplantation: a report from the Center for International Blood and Marrow Transplant 
Research. Biol Blood Marrow Transplant, 2015. 21(2): p. 266-74. 
4. 
Couriel, D., et al., Ancillary therapy and supportive care of chronic graft-versus-host disease: 
national institutes of health consensus development project on criteria for clinical trials in 
chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group 
Report. Biol Blood Marrow Transplant, 2006. 12(4): p. 375-96. 
5. 
Strong Rodrigues, K., et al., Cutaneous Graft-Versus-Host Disease: Diagnosis and 
Treatment. Am J Clin Dermatol, 2018. 19(1): p. 33-50. 
6. 
Ballester-Sanchez, R., et al., Review of Cutaneous Graft-vs-Host Disease. Actas 
Dermosifiliogr, 2016. 107(3): p. 183-93. 
7. 
Choi, C.J. and P. Nghiem, Tacrolimus ointment in the treatment of chronic cutaneous graft-
vs-host disease: a case series of 18 patients. Arch Dermatol, 2001. 137(9): p. 1202-6. 
8. 
Elad, S., et al., Topical tacrolimus--a novel treatment alternative for cutaneous chronic graft-
versus-host disease. Transpl Int, 2003. 16(9): p. 665-70. 
9. 
Meena, S., et al., Topical Corticosteroids Abuse: A Clinical Study of Cutaneous Adverse 
Effects. Indian J Dermatol, 2017. 62(6): p. 675. 
10. 
Hajar, T., et al., A systematic review of topical corticosteroid withdrawal ("steroid addiction") 
in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol, 2015. 72(3): p. 
541-549 e2. 
11. 
Zeiser, R., et al., Ruxolitinib in corticosteroid-refractory graft-versus-host disease after 
allogeneic stem cell transplantation: a multicenter survey. Leukemia, 2015. 29(10): p. 2062-
8. 
12. 
Jagasia, M., et al., Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an 
introduction to the REACH trials. Immunotherapy, 2018. 10(5): p. 391-402. 
13. 
Craiglow, B.G., D. Tavares, and B.A. King, Topical Ruxolitinib for the Treatment of Alopecia 
Universalis. JAMA Dermatol, 2016. 152(4): p. 490-1. 
14. 
Bayart, C.B., et al., Topical Janus kinase inhibitors for the treatment of pediatric alopecia 
areata. J Am Acad Dermatol, 2017. 77(1): p. 167-170. 
15. 
Shreberk-Hassidim, R., Y. Ramot, and A. Zlotogorski, Janus kinase inhibitors in dermatology: 
A systematic review. J Am Acad Dermatol, 2017. 76(4): p. 745-753 e19. 
16. 
Damsky, W. and B.A. King, JAK inhibitors in dermatology: The promise of a new drug class. 
J Am Acad Dermatol, 2017. 76(4): p. 736-744. 
17. 
Punwani, N., et al., Downmodulation of key inflammatory cell markers with a topical Janus 
kinase 1/2 inhibitor. Br J Dermatol, 2015. 173(4): p. 989-97. 
18. 
Rothstein, B., et al., Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J 
Am Acad Dermatol, 2017. 76(6): p. 1054-1060 e1. 
19. 
Kheirkhah, A., et al., A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical 
Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-Associated 
Ocular Surface Disease. Cornea, 2017. 36(7): p. 799-804. 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023

MEMORIAL SLOAN KETTERING CANCER CENTER 
 
 
IRB PROTOCOL 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
Page 38 of 38 
20. 
Takahashi, S., et al., Ruxolitinib protects skin stem cells and maintains skin homeostasis in 
murine graft-versus-host disease. Blood, 2018. 
21. 
Takahashi, S., et al., Topical Ruxolitinib Protects LGR5+Stem Cells in the Hair Follicle and 
Ameliorates Skin Graft-Versus-Host Disease. Biology of Blood and Marrow Transplantation, 
2016. 22(3): p. S21-S22. 
22. 
National Cancer Institute (U.S.), Common terminology criteria for adverse events (CTCAE). 
Rev. ed. NIH publication. 2009, Bethesda, Md.: U.S. Dept. of Health and Human Services, 
National Institutes of Health, National Cancer Institute. 194 p. 
23. 
Incyte, INVESTIGATOR'S BROCHURE: INCB018424 PHOSPHATE CREAM. 2017. 
24. 
Jagasia, M.H., et al., National Institutes of Health Consensus Development Project on 
Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and 
Staging Working Group report. Biol Blood Marrow Transplant, 2015. 21(3): p. 389-401 e1. 
25. 
Lessin, S.R., et al., Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a 
randomized, controlled, multicenter trial testing the efficacy and safety of a novel 
mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol, 2013. 149(1): p. 25-32. 
26. 
Sacco, J.J., et al., The average body surface area of adult cancer patients in the UK: a 
multicentre retrospective study. PLoS One, 2010. 5(1): p. e8933. 
 
 
20.0 
APPENDICES 
 
Appendix I: Adult Body Surface Area Calculator 
 
Appendix II: Pediatric Body Surface Area Calculator 
 
Appendix IIIA: PRO-CTCAE™ (LEFT) 
 
Appendix IIIB: PRO-CTCAE™ (RIGHT) 
 
Appendix IVA: Physician’s Global Assessment of Clinical Condition (PGA) (LEFT) 
 
Appendix IVB: Physician’s Global Assessment of Clinical Condition (PGA) (RIGHT) 
 
Appendix V: Composite Assessment of Index Lesion Severity (CAILS) 
 
Appendix VI: Patient Instructions: Topical Medications 
 
Appendix VII: Patient Medication Application Diary 
 
Appendix VIII: Skin Stripping Instructions 
MSK IRB#: 18-412 A(21), Approval Date: 18-Dec-2023