Acute Myeloid Leukemia, Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia
Conditions
Brief summary
An open-label study available to all eligible participants from Study B1371019 and participants originating from Study B1371012 continuing on study intervention with azacitidine with or without glasdegib.
Interventions
DRUGGlasdegib
25 mg or 100 mg tablet
DRUGAzacitidine
100 mg/vial powder for 25 mg/mL suspension for injection
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Any participant who continues to demonstrate clinical benefit (as determined by the Principal Investigator) from study treatment with azacitidine with or without glasdegib in this Study or from Study B1371012. * Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
Exclusion criteria
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Female participants who are pregnant or breastfeeding (if continuing to receive study intervention); * Participant has been withdrawn from Study B1371019 and Study B1371012 for any reason (including INT cohort participants required to end study treatment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE | From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) | AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). An AE was considered treatment related as assigned by the investigator. |
| Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs | From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) | A SAE was defined as any untoward medical occurrence that, at any dose that resulted in death; was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or other medical events as per investigator's judgement. A SAE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). A SAE was considered treatment related as assigned by the investigator. |
Countries
Austria, Canada, Czechia, France, Hungary, Italy, Japan, Mexico, Poland, Spain, United Kingdom
Participant flow
Recruitment details
Participants from non-intensive (NINT) cohort of study B1371019 (NCT03416179) or study B1371012 (NCT02367456) were enrolled in this open label, continuation study. A total of 14 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Glasdegib + Azacitidine Participants received glasdegib 100 milligrams (mg) tablet per oral (PO) once a day (QD) in combination with azacitidine 75 mg per meter squared (m\^2)/day as subcutaneous (SC) injection or intravenous (IV) infusion for 7 days every 28 days. Treatment continued until objective disease progression or relapse, death, unacceptable toxicity, or participant refusal, whichever occurred first. Participants were followed up for 28 days after end of study treatment. | 9 |
| Placebo + Azacitidine Participants received placebo matched to Glasdegib in combination with azacitidine 75mg/m\^2/day SC or IV for 7 days every 28 days. Treatment continued until objective disease progression or relapse, death, unacceptable toxicity, or participant refusal, whichever occurred first. Participants were followed up for 28 days after end of study treatment. | 5 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Other | 4 | 4 |
| Overall Study | Randomized but not treated | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo + Azacitidine | Total | Glasdegib + Azacitidine |
|---|---|---|---|
| Age, Continuous | 76.80 Years STANDARD_DEVIATION 5.26 | 73.93 Years STANDARD_DEVIATION 4.8 | 72.33 Years STANDARD_DEVIATION 3.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 11 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 0 / 5 |
| other Total, other adverse events | 6 / 9 | 3 / 5 |
| serious Total, serious adverse events | 2 / 9 | 1 / 5 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE
AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). An AE was considered treatment related as assigned by the investigator.
Time frame: From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days)
Population: Safety analysis set included all participants who receive at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Glasdegib + Azacitidine | Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE | Treatment related AE | 5 Participants |
| Glasdegib + Azacitidine | Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE | Treatment emergent AE | 7 Participants |
| Placebo + Azacitidine | Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE | Treatment emergent AE | 4 Participants |
| Placebo + Azacitidine | Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE | Treatment related AE | 4 Participants |
Primary
Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs
A SAE was defined as any untoward medical occurrence that, at any dose that resulted in death; was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or other medical events as per investigator's judgement. A SAE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). A SAE was considered treatment related as assigned by the investigator.
Time frame: From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days)
Population: Safety analysis set included all participants who receive at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Glasdegib + Azacitidine | Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs | Treatment emergent SAEs | 2 Participants |
| Glasdegib + Azacitidine | Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs | Treatment related SAEs | 1 Participants |
| Placebo + Azacitidine | Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs | Treatment emergent SAEs | 1 Participants |
| Placebo + Azacitidine | Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs | Treatment related SAEs | 1 Participants |