| Eligibility |
Inclusion Criteria:
1. Written informed consent signed by the patient or legal guardian prior to any
study-related screening procedures
2. Patients who have undergone allo-hematopoietic stem cell transplant(s) (HSCT) from any
donor HLA type (related or unrelated donor with any degree of HLA matching) using any
graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of
non-myeloablative, myeloablative, and reduced intensity conditions are eligible.
3. Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria:
- Moderate cGVHD: at least 1 organ (except lung) with a score of 2, =3 organs
involved with a score of 1 in each organ, or lung score of 1
- Severe cGVHD: at least 1 organ with a score of 3, or lung score of 2 or 3
4. cGVHD must be refractory to steroids defined by at least one criteria:
- Patient is refractory to glucocorticoid therapy at screening: ongoing treatment
with prednisone equivalent =0.20 mg/kg/day x 4 weeks (wks) at screening and organ
progression documented 4 wks after the initiation of this regimen
- Patient is dependent on glucocorticoid therapy at screening: treatment with a
prednisone equivalent mean dose =0.20 mg/kg/day received for 12 wks at screening
- Patient is intolerant to glucocorticoids at screening: ongoing treatment with
prednisone equivalent =0.20 mg/kg/day x 4 wks at screening and presence of at
least one documented glucocorticoid toxicity
5. Evidence of myeloid and platelet engraftment (absolute neutrophil count ?1,000/mm^3
and platelet count ?25,000/mm^3). Use of growth factors or platelet transfusions is
not allowed within 7 days before screening of laboratory assessment.
6. Patients must currently be receiving systemic or other immunosuppressive therapies for
the treatment of cGVHD for a duration of ?6 months prior to start of study treatment
7. Patients must be able to swallow and retain oral medication
8. Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
9. Adequate hematologic function
10. Adequate renal function: creatinine clearance =30 mL/min measured or calculated by
Cockcroft Gault equation
11. Patients willing to avoid pregnancy or father children based on 1 of the following:
- Women of non-childbearing potential (i.e., surgically sterile by hysterectomy
and/or bilateral oophorectomy OR =12 months of amenorrhea)
- Women of childbearing potential who have a negative serum pregnancy test at
screening and who agree to take appropriate precautions to avoid pregnancy from
screening through safety follow-up.
- Men who agree to take appropriate precautions to avoid fathering children from
screening through safety follow-up. Male patients must also refrain from donating
sperm during their participation in the study and for at least 3 months after
completing the study.
12. Ability to understand the nature of this study and to comply with study and follow-up
procedures
Exclusion Criteria:
1. Receiving concomitant JAK inhibitor for cGVHD; prior treatment with a JAK inhibitor
for acute GVHD is permitted if treatment was stopped more than 60 days prior to study
start. Patients are eligible if JAK inhibitors for treatment of cGVHD are stopped due
to side effects and not due to refractoriness.
2. Treatment with any other investigational agent, device, or procedure, within 28 days
(or 5 half-lives, whichever is longer) of enrollment. For previous study drugs where 5
half-lives is =28 days, a minimum of 10 days between termination of that study drug
and administration of itacitinib is required.
3. Presence of current secondary malignancies with the exception of previously treated in
situ carcinoma, cervical carcinoma Stage 1B or less, and noninvasive basal cell or
squamous cell skin carcinoma.
4. Pregnant or nursing (lactating) women
5. Patients with relapsed primary malignancy, or who have been treated for relapse after
the allo-HSCT was performed
6. History of progressive multifocal leukoencephalopathy
7. Evidence of the following infections:
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections
are considered controlled if appropriate therapy has been instituted and, at the
time of screening, no signs of infection progression are present. Progression of
infection is defined as hemodynamic instability attributable to sepsis, new
symptoms, worsening physical signs or radiographic findings attributable to
infection. Persisting fever without other signs or symptoms will not be
interpreted as progressing infection.
- Known HIV infection
- Active tuberculosis infection that developed after allo-HSCT
- Active viral infection confirmed by polymerase chain reaction for the BK virus (
a polyoma virus), cytomegalovirus, Epstein-Barr virus, and human herpes virus 6
- Active hepatitis B virus (HBV) or hepatitis C virus that requires treatment, or
at risk for HBV reactivation (i.e., positive HBsAg)
8. Severe organ dysfunction unrelated to underlying GVHD including:
- Cholestatic disorders or unresolved veno-occlusive disease of the liver
(persistent bilirubin abnormalities not attributable to GVHD and ongoing organ
dysfunction)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral itacitinib (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, or small bowl resection)
- Clinically significant or uncontrolled cardiac disease, including unstable
angina, acute myocardial infarction within 6 months of enrollment, New York Heart
Association Class III or IV congestive heart failure, circulatory collapse
requiring vasopressor or inotropic support, or arrhythmia that requires therapy
- Significant respiratory disease that requires mechanical ventilation support or a
resting O2 saturation ?90 percent by pulse oximetry or FEV1 ?30 percent
9. Patients requiring platelet transfusions to maintain a platelet count ?25,000/mm^3
10. Any corticosteroid therapy for indications other than cGVHD at doses ?1 mg/kg/day
methylprednisone or equivalent within 7 days of study start
11. Patients receiving treatment with medications that interfere with coagulation or
platelet function including, but not limited to, aspirin dose exceeding 81 mg/day and
related drugs such as heparin or warfarin sodium. Use of low molecular weight heparin
is allowed.
12. Known allergies, hypersensitivity, or intolerance to itacitinib or any of its
excipients
13. Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol
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