Chronic Graft Versus Host Disease, Fasciitis
Conditions
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.
Interventions
DRUGGlasdegib
Given PO
Sponsors
Pfizer
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | From the start of treatment through 28 days after stopping study drug (Up to 25 months total) | Safety assessments will consist of monitoring and recording adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | Up to 12 months after the starting glasdegib | ORR will be calculated according to the response definitions of the NIH Consensus Conference. |
| Failure-free Survival | At 12 months | 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. |
| Symptom Burden Assessment - Absolute Change | 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.] | 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 |
| Overall Response Rate (ORR) in Sclerotic Manifestations | Up to 12 months after starting glasdegib | 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. |
| Biologic Impact of Hedgehog Pathway Inhibition | Up to 12 months | Banking of blood and skin biopsy material for future biologic studies of hedgehog pathway inhibition. |
| Symptom Burden Assessment - Clinically Meaningful Change | 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.] | 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 |
| Quality of Life Assessment - Clinically Meaningful Change | 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.] | 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. |
| Quality of Life Assessment | 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.] | 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. |
Countries
United States
Participant flow
Recruitment details
Potentially eligible patients were approached at participating study centers during clinic visits.
Pre-assignment details
After the participant signed and dated the Informed Consent Form (ICF), screening began. Once all screening procedures were completed and eligibility was confirmed, the participant was enrolled into the study. The screening period lasted from the date the participant signed consent until they completed the enrollment visit and started study drug.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Glasdegib) 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.
Glasdegib: Given PO | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | relapse of primary disease | 1 |
| Overall Study | toxicity and/or lack of efficacy | 13 |
Baseline characteristics
| Characteristic | Treatment (Glasdegib) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 64.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 15 |
| other Total, other adverse events | 9 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
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)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Glasdegib) | Number of Participants Who Experienced an Adverse Event | Participants with an SAE and a non-serious AE | 3 Participants |
| Treatment (Glasdegib) | Number of Participants Who Experienced an Adverse Event | Participants with a non-serious AE only | 6 Participants |
| Treatment (Glasdegib) | Number of Participants Who Experienced an Adverse Event | Participants without any adverse events | 6 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Glasdegib) | Biologic Impact of Hedgehog Pathway Inhibition | 15 Participants |
Secondary
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
Population: Five patients censored because they left the study before month 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Glasdegib) | Failure-free Survival | 37 percentage |
Secondary
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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for sclerotic manifestations | partial response | 8 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for all manifestations of chronic GVHD | partial response | 8 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for all manifestations of chronic GVHD | mixed response | 1 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for all manifestations of chronic GVHD | unchanged | 5 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for all manifestations of chronic GVHD | progressive | 1 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for sclerotic manifestations | mixed response | 1 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for sclerotic manifestations | unchanged | 5 Participants |
| Treatment (Glasdegib) | ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations | ORR for sclerotic manifestations | progressive | 1 Participants |
Secondary
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Glasdegib) | Overall Response Rate (ORR) in Sclerotic Manifestations | Partial response | 7 Participants |
| Treatment (Glasdegib) | Overall Response Rate (ORR) in Sclerotic Manifestations | Mixed response | 1 Participants |
| Treatment (Glasdegib) | Overall Response Rate (ORR) in Sclerotic Manifestations | Unchanged | 6 Participants |
| Treatment (Glasdegib) | Overall Response Rate (ORR) in Sclerotic Manifestations | Progressive | 1 Participants |
Secondary
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.]
Population: Data not available for 5 participants at Cycle 4 and 4 participants for End of Treatment (EOT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Depression absolute change | 0.2 score on a scale | Standard Error 5 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Ability to Participate in Social Roles absolute change | 2.1 score on a scale | Standard Error 7.4 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Physical Function absolute change | 0.3 score on a scale | Standard Error 5.2 |
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Anxiety absolute change | 0.8 score on a scale | Standard Error 5.3 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Pain Interference absolute change | -1.8 score on a scale | Standard Error 9.9 |
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Ability to Participate in Social Roles absolute change | -0.5 score on a scale | Standard Error 5.1 |
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Physical Function absolute change | -0.1 score on a scale | Standard Error 4.9 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Depression absolute change | 0.3 score on a scale | Standard Error 8.2 |
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Pain Interference absolute change | 3.1 score on a scale | Standard Error 8.7 |
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Sleep Disturbance absolute change | 1.3 score on a scale | Standard Error 5 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Fatigue absolute change | -0.4 score on a scale | Standard Error 6.8 |
| Treatment (Glasdegib) | Quality of Life Assessment | End of Treatment - Fatigue absolute change | -1.7 score on a scale | Standard Error 5.1 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Sleep Disturbance absolute change | 0.5 score on a scale | Standard Error 5.5 |
| Treatment (Glasdegib) | Quality of Life Assessment | Cycle 4 (day 85) - Anxiety absolute change | 2.1 score on a scale | Standard Error 5.9 |
| CR+PR | Quality of Life Assessment | End of Treatment - Fatigue absolute change | -0.7 score on a scale | Standard Error 4.1 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Physical Function absolute change | 0.8 score on a scale | Standard Error 6.2 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Anxiety absolute change | 1.6 score on a scale | Standard Error 6.8 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Depression absolute change | -0.6 score on a scale | Standard Error 9.6 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Sleep Disturbance absolute change | 1.4 score on a scale | Standard Error 5.8 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Ability to Participate in Social Roles absolute change | 2.7 score on a scale | Standard Error 8.9 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Pain Interference absolute change | -5.8 score on a scale | Standard Error 7.7 |
| CR+PR | Quality of Life Assessment | End of Treatment - Physical Function absolute change | -0.1 score on a scale | Standard Error 6 |
| CR+PR | Quality of Life Assessment | End of Treatment - Anxiety absolute change | 2.5 score on a scale | Standard Error 4.4 |
| CR+PR | Quality of Life Assessment | End of Treatment - Depression absolute change | -0.2 score on a scale | Standard Error 5.7 |
| CR+PR | Quality of Life Assessment | Cycle 4 (day 85) - Fatigue absolute change | -2.7 score on a scale | Standard Error 6.7 |
| CR+PR | Quality of Life Assessment | End of Treatment - Sleep Disturbance absolute change | 0.3 score on a scale | Standard Error 4.1 |
| CR+PR | Quality of Life Assessment | End of Treatment - Ability to Participate in Social Roles absolute change | -2.3 score on a scale | Standard Error 5.5 |
| CR+PR | Quality of Life Assessment | End of Treatment - Pain Interference absolute change | 2.4 score on a scale | Standard Error 9.2 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Pain Interference absolute change | 4.4 score on a scale | Standard Error 9 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Depression absolute change | 1.0 score on a scale | Standard Error 4 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Fatigue absolute change | 4.9 score on a scale | Standard Error 3.7 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Ability to Participate in Social Roles absolute change | 2.7 score on a scale | Standard Error 2 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Fatigue absolute change | -3.5 score on a scale | Standard Error 6.8 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Depression absolute change | 2.2 score on a scale | Standard Error 3.9 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Physical Function absolute change | -0.9 score on a scale | Standard Error 2.2 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Pain Interference absolute change | 7.6 score on a scale | Standard Error 8.7 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Sleep Disturbance absolute change | 2.9 score on a scale | Standard Error 6.7 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Physical Function absolute change | 0.1 score on a scale | Standard Error 2.5 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Ability to Participate in Social Roles absolute change | 0.6 score on a scale | Standard Error 2.8 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Anxiety absolute change | 3.4 score on a scale | Standard Error 3.9 |
| MR+SD+PD | Quality of Life Assessment | End of Treatment - Anxiety absolute change | -2.1 score on a scale | Standard Error 6 |
| MR+SD+PD | Quality of Life Assessment | Cycle 4 (day 85) - Sleep Disturbance absolute change | -1.6 score on a scale | Standard Error 5 |
Secondary
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.]
Population: Data not available for 5 and 4 participants at the Cycle 4 and End of Treatment (EOT) visits, respectively.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | Worse | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | No change | 6 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | Worse | 3 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | No change | 8 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | Worse | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | No change | 10 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | Better | 3 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | No change | 6 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | Worse | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | No change | 6 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | No change | 7 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | No change | 9 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | Worse | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | Better | 0 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | Better | 3 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | Worse | 3 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | Worse | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | No change | 5 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | No change | 8 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | Better | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | Better | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | Worse | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | Worse | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | No change | 6 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | No change | 8 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | Worse | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | No change | 8 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | Better | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | Worse | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | Worse | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | No change | 7 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | No change | 8 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | Worse | 2 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | Worse | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | Better | 1 Participants |
| Treatment (Glasdegib) | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | Better | 2 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | No change | 6 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | Worse | 0 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | No change | 5 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | No change | 4 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | Worse | 2 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | Better | 2 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | No change | 4 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | No change | 5 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | No change | 4 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | Worse | 2 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | Better | 3 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | No change | 3 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | Better | 3 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | No change | 4 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | Worse | 0 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | No change | 5 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | Better | 0 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | No change | 5 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | Worse | 2 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | No change | 5 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | Better | 0 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | No change | 6 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | Better | 0 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | No change | 6 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | Worse | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | Better | 1 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | No change | 4 Participants |
| CR+PR | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | Worse | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | Worse | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | Worse | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | No change | 4 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | No change | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | No change | 3 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Fatigue clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | No change | 3 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Depression clinically meaningful change | Worse | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | Worse | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | Better | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | No change | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | No change | 3 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | No change | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85)- Depression clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | No change | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Fatigue clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | Worse | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Pain Interference clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | No change | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | Better | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Pain Interference clinically meaningful change | Worse | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Sleep Disturbance clinically meaningful change | Worse | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | No change | 3 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | No change | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | No change | 4 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Ability to Participate in Social Roles clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Physical Function clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Physical Function clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | Worse | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Ability to Participate in Social Roles clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | Better | 1 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | No change | 2 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Anxiety clinically meaningful change | Better | 0 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | End of Treatment - Anxiety clinically meaningful change | No change | 3 Participants |
| MR+SD+PD | Quality of Life Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) - Sleep Disturbance clinically meaningful change | Better | 1 Participants |
Secondary
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.]
Population: Data not available for 5 and 4 participants for the Cycle 4 and End of Treatment visits, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Glasdegib) | Symptom Burden Assessment - Absolute Change | Cycle 4 (Day 85) | 2.5 score on a scale | Standard Deviation 6.9 |
| Treatment (Glasdegib) | Symptom Burden Assessment - Absolute Change | End of Treatment | 2.8 score on a scale | Standard Deviation 9.9 |
| CR+PR | Symptom Burden Assessment - Absolute Change | Cycle 4 (Day 85) | 4.9 score on a scale | Standard Deviation 6.9 |
| CR+PR | Symptom Burden Assessment - Absolute Change | End of Treatment | 6.8 score on a scale | Standard Deviation 10.5 |
| MR+SD+PD | Symptom Burden Assessment - Absolute Change | Cycle 4 (Day 85) | -3.0 score on a scale | Standard Deviation 1.5 |
| MR+SD+PD | Symptom Burden Assessment - Absolute Change | End of Treatment | -4.1 score on a scale | Standard Deviation 1.8 |
Secondary
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.]
Population: Data not available for 5 and 4 participants at the Cycle 4 and End of Treatment (EOT) visits, respectively.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment (Glasdegib) | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | Worse | 4 Participants |
| Treatment (Glasdegib) | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | No change | 5 Participants |
| Treatment (Glasdegib) | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | Worse | 4 Participants |
| Treatment (Glasdegib) | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | No change | 6 Participants |
| Treatment (Glasdegib) | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | Better | 2 Participants |
| Treatment (Glasdegib) | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | Better | 0 Participants |
| CR+PR | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | Better | 1 Participants |
| CR+PR | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | No change | 2 Participants |
| CR+PR | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | Better | 0 Participants |
| CR+PR | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | Worse | 4 Participants |
| CR+PR | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | Worse | 4 Participants |
| CR+PR | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | No change | 3 Participants |
| MR+SD+PD | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | Worse | 0 Participants |
| MR+SD+PD | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | Better | 0 Participants |
| MR+SD+PD | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | No change | 0 Participants |
| MR+SD+PD | Symptom Burden Assessment - Clinically Meaningful Change | Cycle 4 (Day 85) | Worse | 3 Participants |
| MR+SD+PD | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | Better | 1 Participants |
| MR+SD+PD | Symptom Burden Assessment - Clinically Meaningful Change | End of Treatment | No change | 3 Participants |