A Phase 1/2 interventional study of Glasdegib in Chronic Graft Versus Host Disease and Fasciitis, sponsored by Fred Hutchinson Cancer Center. Terminated at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-29.
Sponsored by Fred Hutchinson Cancer Center · Phase 1/2, Interventional, and Treatment
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.
235 studies on the registry are indexed under Fasciitis; 37 are open to participants now.
This study's enrollment of 15 is below the median of 54 across 192 interventional studies indexed under Fasciitis.
Browse Fasciitis studies →Fred Hutchinson Cancer Center is the lead sponsor of 537 studies on the registry; 79 are open to participants now.
Of its 57 completed or terminated interventional studies of FDA-regulated products, 45 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Diagnosed with cGVHD-related sclerosis or fasciitis
Female patients who:
Male patients who:
Exclusion Criteria:
Known organ dysfunction
Addition of any new systemic immunosuppressive treatment within the last 2 weeks
* Addition of new systemic immunosuppressive treatment along with glasdegib is also prohibited
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
Non-hematologic malignancy within the past 2 years with the exception of:
Patients receive glasdegib PO QD on days 1-28. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Drug: Glasdegib
Given PO
Also known as: 1095173-27-5, PF 04449913, PF-04449913, PF04449913
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
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.]
Potentially eligible patients were approached at participating study centers during clinic visits.
| Milestone | Treatment (Glasdegib) |
|---|---|
| Started | 15 |
| Completed | 1 |
| Not completed | 14 |
| Withdrew: Relapse of primary disease | 1 |
| Withdrew: Toxicity and/or lack of efficacy | 13 |
Safety assessments will consist of monitoring and recording adverse events.
| Participants | Treatment (Glasdegib) |
|---|---|
| Participants with an SAE and a non-serious AE | 3 |
| Participants with a non-serious AE only | 6 |
| Participants without any adverse events | 6 |
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.
| Participants | Treatment (Glasdegib) |
|---|---|
| Partial response | 7 |
| Mixed response | 1 |
| Unchanged | 6 |
| Progressive | 1 |
ORR will be calculated according to the response definitions of the NIH Consensus Conference.
| Participants | Treatment (Glasdegib) |
|---|---|
| ORR for all manifestations of chronic GVHD — partial response | 8 |
| ORR for all manifestations of chronic GVHD — mixed response | 1 |
| ORR for all manifestations of chronic GVHD — unchanged | 5 |
| ORR for all manifestations of chronic GVHD — progressive | 1 |
| ORR for sclerotic manifestations — partial response | 8 |
| ORR for sclerotic manifestations — mixed response | 1 |
| ORR for sclerotic manifestations — unchanged | 5 |
| ORR for sclerotic manifestations — progressive | 1 |
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.
| percentage | Treatment (Glasdegib) |
|---|---|
| Failure-free Survival | 37 (10 to 64) |
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
| score on a scale | Treatment (Glasdegib), All | CR+PR | MR+SD+PD |
|---|---|---|---|
| Cycle 4 (Day 85) | 2.5 ± 6.9 | 4.9 ± 6.9 | -3.0 ± 1.5 |
| End of Treatment | 2.8 ± 9.9 | 6.8 ± 10.5 | -4.1 ± 1.8 |
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.
| score on a scale | Treatment (Glasdegib), All | CR+PR | MR+SD+PD |
|---|---|---|---|
| Cycle 4 (day 85) - Physical Function absolute change | 0.3 ± 5.2 | 0.8 ± 6.2 | -0.9 ± 2.2 |
| Cycle 4 (day 85) - Anxiety absolute change | 2.1 ± 5.9 | 1.6 ± 6.8 | 3.4 ± 3.9 |
| Cycle 4 (day 85) - Depression absolute change | 0.3 ± 8.2 | -0.6 ± 9.6 | 2.2 ± 3.9 |
| Cycle 4 (day 85) - Fatigue absolute change | -0.4 ± 6.8 | -2.7 ± 6.7 | 4.9 ± 3.7 |
| Cycle 4 (day 85) - Sleep Disturbance absolute change | 0.5 ± 5.5 | 1.4 ± 5.8 | -1.6 ± 5.0 |
| Cycle 4 (day 85) - Ability to Participate in Social Roles absolute change | 2.1 ± 7.4 | 2.7 ± 8.9 | 0.6 ± 2.8 |
| Cycle 4 (day 85) - Pain Interference absolute change | -1.8 ± 9.9 | -5.8 ± 7.7 | 7.6 ± 8.7 |
| End of Treatment - Physical Function absolute change | -0.1 ± 4.9 | -0.1 ± 6.0 | 0.1 ± 2.5 |
| End of Treatment - Anxiety absolute change | 0.8 ± 5.3 | 2.5 ± 4.4 | -2.1 ± 6.0 |
| End of Treatment - Depression absolute change | 0.2 ± 5.0 | -0.2 ± 5.7 | 1.0 ± 4.0 |
| End of Treatment - Fatigue absolute change | -1.7 ± 5.1 | -0.7 ± 4.1 | -3.5 ± 6.8 |
| End of Treatment - Sleep Disturbance absolute change | 1.3 ± 5.0 | 0.3 ± 4.1 | 2.9 ± 6.7 |
| End of Treatment - Ability to Participate in Social Roles absolute change | -0.5 ± 5.1 | -2.3 ± 5.5 | 2.7 ± 2.0 |
| End of Treatment - Pain Interference absolute change | 3.1 ± 8.7 | 2.4 ± 9.2 | 4.4 ± 9.0 |
Banking of blood and skin biopsy material for future biologic studies of hedgehog pathway inhibition.
| Participants | Treatment (Glasdegib) |
|---|---|
| Biologic Impact of Hedgehog Pathway Inhibition | 15 |
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
| Participants | Treatment (Glasdegib), All | CR+PR | MR+SD+PD |
|---|---|---|---|
| Cycle 4 (Day 85) — Better | 0 | 0 | 0 |
| Cycle 4 (Day 85) — No change | 6 | 3 | 0 |
| Cycle 4 (Day 85) — Worse | 4 | 4 | 3 |
| End of Treatment — Better | 2 | 1 | 1 |
| End of Treatment — No change | 5 | 2 | 3 |
| End of Treatment — Worse | 4 | 4 | 0 |
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.
| Participants | Treatment (Glasdegib), All | CR+PR | MR+SD+PD |
|---|---|---|---|
| Cycle 4 (Day 85) - Physical Function clinically meaningful change — Better | 1 | 1 | 0 |
| Cycle 4 (Day 85) - Physical Function clinically meaningful change — No change | 8 | 5 | 3 |
| Cycle 4 (Day 85) - Physical Function clinically meaningful change — Worse | 1 | 1 | 0 |
| Cycle 4 (Day 85) - Anxiety clinically meaningful change — Better | 1 | 1 | 0 |
| Cycle 4 (Day 85) - Anxiety clinically meaningful change — No change | 6 | 4 | 2 |
| Cycle 4 (Day 85) - Anxiety clinically meaningful change — Worse | 3 | 2 | 1 |
| Cycle 4 (Day 85)- Depression clinically meaningful change — Better | 2 | 2 | 0 |
| Cycle 4 (Day 85)- Depression clinically meaningful change — No change | 6 | 4 | 2 |
| Cycle 4 (Day 85)- Depression clinically meaningful change — Worse | 2 | 1 | 1 |
| Cycle 4 (Day 85)- Fatigue clinically meaningful change — Better | 1 | 1 | 0 |
| Cycle 4 (Day 85)- Fatigue clinically meaningful change — No change | 7 | 5 | 2 |
| Cycle 4 (Day 85)- Fatigue clinically meaningful change — Worse | 2 | 1 | 1 |
| Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change — Better | 2 | 1 | 1 |
| Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change — No change | 6 | 4 | 2 |
| Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change — Worse | 2 | 2 | 0 |
| Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change — Better | 3 | 3 | 0 |
| Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change — No change | 6 | 3 | 3 |
| Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change — Worse | 1 | 1 | 0 |
| Cycle 4 (Day 85) - Pain Interference clinically meaningful change — Better | 3 | 3 | 0 |
| Cycle 4 (Day 85) - Pain Interference clinically meaningful change — No change | 5 | 4 | 1 |
| Cycle 4 (Day 85) - Pain Interference clinically meaningful change — Worse | 2 | 0 | 2 |
| End of Treatment - Physical Function clinically meaningful change — Better | 1 | 1 | 0 |
| End of Treatment - Physical Function clinically meaningful change — No change | 9 | 5 | 4 |
| End of Treatment - Physical Function clinically meaningful change — Worse | 1 | 1 | 0 |
| End of Treatment - Anxiety clinically meaningful change — Better | 1 | 0 | 1 |
| End of Treatment - Anxiety clinically meaningful change — No change | 8 | 5 | 3 |
| End of Treatment - Anxiety clinically meaningful change — Worse | 2 | 2 | 0 |
| End of Treatment - Depression clinically meaningful change — Better | 1 | 1 | 0 |
| End of Treatment - Depression clinically meaningful change — No change | 8 | 5 | 3 |
| End of Treatment - Depression clinically meaningful change — Worse | 2 | 1 | 1 |
| End of Treatment - Fatigue clinically meaningful change — Better | 2 | 0 | 2 |
| End of Treatment - Fatigue clinically meaningful change — No change | 8 | 6 | 2 |
| End of Treatment - Fatigue clinically meaningful change — Worse | 1 | 1 | 0 |
| End of Treatment - Sleep Disturbance clinically meaningful change — Better | 2 | 1 | 1 |
| End of Treatment - Sleep Disturbance clinically meaningful change — No change | 8 | 6 | 2 |
| End of Treatment - Sleep Disturbance clinically meaningful change — Worse | 1 | 0 | 1 |
| End of Treatment - Ability to Participate in Social Roles clinically meaningful change — Better | 0 | 0 | 0 |
| End of Treatment - Ability to Participate in Social Roles clinically meaningful change — No change | 10 | 6 | 4 |
| End of Treatment - Ability to Participate in Social Roles clinically meaningful change — Worse | 1 | 1 | 0 |
| End of Treatment - Pain Interference clinically meaningful change — Better | 1 | 1 | 0 |
| End of Treatment - Pain Interference clinically meaningful change — No change | 7 | 4 | 3 |
| End of Treatment - Pain Interference clinically meaningful change — Worse | 3 | 2 | 1 |
Collected over The AE reporting period for this study began when the participant received their first dose of study drug and ended with the EOT visit, or 28 days after the last dose of study drug, whichever was later. Exceptions to this reporting period were (a) any AE occurring due to a protocol-specific screening procedure; and (b) any SAE occuring beyond 28 days after the last dose of glasdegib AND assessed by the investigator as possibly related to glasdegib.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Glasdegib) | 2/15 (13.3%) | 3/15 (20%) | 9/15 (60%) |
| Event | Treatment (Glasdegib) |
|---|---|
| acute myopathyMusculoskeletal and connective tissue disorders | 1/15 |
| upper respiratory infectionInfections and infestations | 1/15 |
| mastitisInfections and infestations | 1/15 |
| Event | Treatment (Glasdegib) |
|---|---|
| muscle crampingMusculoskeletal and connective tissue disorders | 5/15 |
| hyponatremiaMetabolism and nutrition disorders | 2/15 |
| hypokalemiaMetabolism and nutrition disorders | 2/15 |
| myalgiaMusculoskeletal and connective tissue disorders | 1/15 |
| Age, Categorical(Participants) | Treatment (Glasdegib) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 8 |
| >=65 years | 7 |
| Age, Continuous(years) | Treatment (Glasdegib) |
|---|---|
| Median | 64.0 (33 to 74) |
| Sex: Female, Male(Participants) | Treatment (Glasdegib) |
|---|---|
| Female | 8 |
| Male | 7 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Glasdegib) |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 14 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Treatment (Glasdegib) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 0 |
| White | 13 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Treatment (Glasdegib) |
|---|---|
| United States | 15 |
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