Glasdegib for Chronic Graft-Versus-Host Disease
Glasdegib for Chronic Graft-Versus-Host Disease
This phase I/II trial studies whether glasdegib is helpful in treating sclerosis associated
 with chronic graft-versus-host disease. It will also investigate the safety of glasdegib in
 treating patients with chronic graft-versus-host disease.
OUTLINE: This is a phase I/II study.

 Patients receive glasdegib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28
 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Inclusion Criteria:

 -  Diagnosed with moderate or severe cGVHD according to the 2014 National Institute of
 Health (NIH) Consensus Criteria

 -  Diagnosed with cGVHD-related sclerosis or fasciitis

 -  Skin feature score of at least 2 OR

 -  Joints and fascia score of at least 1

 -  Stable or progressive sclerosis/fasciitis despite treatment with at least one prior
 line of systemic therapy for cGVHD

 -  Female patients who:

 -  Are documented to be postmenopausal or are surgically sterile, OR

 -  If of childbearing potential, agree to use at least 1 highly effective method of
 contraception from the time of signing the informed consent form through 30 days
 after the last dose of study drug, OR agree to practice true abstinence or
 exclusively non-heterosexual activity when this is in line with the preferred and
 usual lifestyle of the subject

 -  Male patients who:

 -  Are surgically sterile (vasectomized) OR

 -  Agree to use at least 1 highly effective method of contraception during the
 entire study treatment period and through 30 days after the last dose of study
 drug, OR agree to practice true abstinence or exclusively non-heterosexual
 activity when this is in line with the preferred and usual lifestyle of the
 subject, AND

 -  Agree to use a condom to prevent potential transmission of investigational drug
 in seminal fluid

 -  Absolute neutrophil count (ANC) > 1000/uL

 -  Platelet count > 50 x 10^9/mL

 -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 x upper limit
 of normal (ULN) unless attributed to cGVHD

 -  Normal total bilirubin unless attributed to cGVHD

 -  Creatinine < 2.0 mg/dl

 Exclusion Criteria:

 -  Hospitalization for evaluation or management of an infection within the last 8 weeks

 -  Known organ dysfunction

 -  Uncontrolled cardiovascular disease, including arrhythmias, congestive heart
 failure

 -  Oxygen requirement

 -  Addition of any new systemic immunosuppressive treatment within the last 2 weeks

 * Addition of new systemic immunosuppressive treatment along with glasdegib is also
 prohibited

 -  Corrected QT (QTc) interval > 480 ms

 -  Female patients who are lactating or have a positive serum pregnancy test

 -  Major surgery within 14 days before enrollment

 * Does not include placement of venous access device, bone marrow biopsy, GVHD
 diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation
 care

 -  Use of any concomitant medications meds that are prohibited within the past 7 days

 -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
 potentially interfere with the completion of treatment according to this protocol

 -  Known intolerance to glasdegib, sonidegib, or vismodegib

 -  Non-hematologic malignancy within the past 2 years with the exception of:

 -  Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid
 cancer

 -  Carcinoma in situ of the cervix or breast

 -  Prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen
 levels

 -  Cancer considered cured by surgical resection or unlikely to impact survival
 during the duration of the study

 -  Treatment with non-Food and Drug Administration (FDA) approved drug within 21 days of
 start of this trial

 -  Evidence of recurrent or progressive underlying malignant disease

 -  Karnofsky performance status < 70%

 -  History of non-compliance

 -  Life expectancy < 6 months

 -  Grade 2 or 3 muscle cramping, or grade 1 muscle cramping that occurs at least weekly