Clinical trial NCT04111497: Glasdegib for Chronic Graft-Versus-Host Disease
Official title: A Single-Arm, Open-Label, Phase I/II Study of Glasdegib for Sclerotic Chronic Graft-Vs-Host Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Chronic Graft Versus Host Disease
Fasciitis
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2019-10-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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
* New, 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

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event
timeFrame: From the start of treatment through 28 days after stopping study drug (Up to 25 months total)
Secondary outcomes:
measure: Overall Response Rate (ORR) in Sclerotic Manifestations
timeFrame: Up to 12 months after starting glasdegib
measure: ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations
timeFrame: Up to 12 months after the starting glasdegib
measure: Failure-free Survival
timeFrame: At 12 months
measure: Symptom Burden Assessment - Absolute Change
timeFrame: Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253), they are not presented.]
measure: Quality of Life Assessment
timeFrame: Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253) they are not presented.]
measure: Biologic Impact of Hedgehog Pathway Inhibition
timeFrame: Up to 12 months
measure: Symptom Burden Assessment - Clinically Meaningful Change
timeFrame: Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253), they are not presented.]
measure: Quality of Life Assessment - Clinically Meaningful Change
timeFrame: Cycle 4 (Day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253) they are not presented.]
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Stephanie Lee
role: PRINCIPAL_INVESTIGATOR
References: