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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Given PO
Duke University Medical Center
Durham, North Carolina, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Number of Participants Who Experienced an Adverse Event
Safety assessments will consist of monitoring and recording adverse events.
Time frame: From the start of treatment through 28 days after stopping study drug (Up to 25 months total)
Overall Response Rate (ORR) in Sclerotic Manifestations
ORR will be calculated according to (1) the response definitions of the National Institute of Health (NIH) Consensus Conference for (a) skin or joint scores (0-3), where improvement by at least 1 point is a partial response (PR) and return to score 0 is a complete response (CR), or (b) the photographic range of motion scale (0-25) where improvement by at least 1 point is a PR and return to score 25 is a CR; and (2) change in the 0-10 sclerotic severity scale where at least a 2 point improvement is a PR or return to 0 (CR). Non-responders are those with mixed response (improvement in one regard and worsening in another), unchanged (stable), and progression.
Time frame: Up to 12 months after starting glasdegib
ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations
ORR will be calculated according to the response definitions of the NIH Consensus Conference.
Time frame: Up to 12 months after the starting glasdegib
Failure-free Survival
Failure-free survival will be estimated using the Kaplan-Meier method (product limit estimator), with death, relapse, or start of another systemic immunosuppressive agent considered as events. Patients lost to follow-up or who withdraw consent will be censored.
Time frame: At 12 months
Symptom Burden Assessment - Absolute Change
Subjects will provide assessments of their symptom burden using a validated instrument recommended by the NIH Consensus on Chronic GVHD (Lee Chronic GVHD Symptom Scale). These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Summary scores will be calculated based on published algorithms with absolute changes from baseline and clinically meaningful changes described for the population as a whole and based on CR+PR versus (vs.) stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis. Lee Symptom Scale: minimum 0, maximum 100; higher score is worse outcome. Due to lack of adequate data at cycles 7 and 10, only Cycle 4 and End of Treatment are presented
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 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.]
Quality of Life Assessment
Subjects will provide assessments of their quality of life using the NIH-endorsed Patient Reported Outcomes Measurement Information System (PROMIS)-29. These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Scores will be calculated based on published algorithms with absolute changes from baseline for the population as a whole and based on CR+PR versus stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis. PROMIS-29 theoretical minimums and maximums are as follows: Physical Function: 22.5-57.0 Depression: 41.0-79.4 Anxiety: 40.3-81.6 Sleep Disturbance: 32.0-73.3 Fatigue: 33.7-75.8 Ability to Participate in Social Roles: 27.5-64.2 Pain Interference: 41.6-75.6 Higher score means a better outcome for Physical Function, Sleep Disturbance, and Social Roles. Higher score means a worse outcome for Anxiety, Depression, Fatigue, and Pain Interference.
Time frame: 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.]
Biologic Impact of Hedgehog Pathway Inhibition
Banking of blood and skin biopsy material for future biologic studies of hedgehog pathway inhibition.
Time frame: Up to 12 months
Symptom Burden Assessment - Clinically Meaningful Change
Subjects will provide assessments of their symptom burden using a validated instrument recommended by the NIH Consensus on Chronic GVHD (Lee Chronic GVHD Symptom Scale). These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Summary scores will be calculated based on published algorithms with absolute changes from baseline and clinically meaningful changes described for the population as a whole and based on CR+PR versus (vs.) stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis. Lee Symptom Scale: minimum 0, maximum 100; higher score is worse outcome. Due to lack of adequate data at cycles 7 and 10, only Cycle 4 and End of Treatment are presented
Time frame: 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.]
Quality of Life Assessment - Clinically Meaningful Change
Subjects will provide assessments of their quality of life using the NIH-endorsed Patient Reported Outcomes Measurement Information System (PROMIS)-29. These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Scores for physical functioning will be calculated based on published algorithms with clinically meaningful changes described for the population as a whole and based on CR+PR versus (vs.) stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis. PROMIS-29 minimums and maximums as follows: Physical Function: 22.5-57.0 Depression: 41.0-79.4 Anxiety: 40.3-81.6 Sleep Disturbance: 32.0-73.3 Fatigue: 33.7-75.8 Ability to Participate in Social Roles: 27.5-64.2 Pain Interference: 41.6-75.6 Higher score means a better outcome for Physical Function, Sleep, and Social Roles. Higher score means a worse outcome for Anxiety, Depression, Fatigue, and Pain.
Time frame: 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.]