Trial Outcomes & Findings for Continuation Study of B1371019(NCT03416179) and B1371012(NCT02367456) Evaluating Azacitidine With Or Without Glasdegib In Patients With Previously Untreated AML, MDS or CMML (NCT NCT04842604)

Last Updated: 2023-12-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

14 participants

Primary outcome timeframe

From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days)

Results posted on

2023-12-18

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	9	5
Overall Study Treated	8	5
Overall Study COMPLETED	3	1
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Death	1	0
Overall Study Other	4	4
Overall Study Randomized but not treated	1	0

Baseline Characteristics

Continuation Study of B1371019(NCT03416179) and B1371012(NCT02367456) Evaluating Azacitidine With Or Without Glasdegib In Patients With Previously Untreated AML, MDS or CMML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glasdegib + Azacitidine n=9 Participants 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.	Placebo + Azacitidine n=5 Participants 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.	Total n=14 Participants Total of all reporting groups
Age, Continuous	72.33 Years STANDARD_DEVIATION 3.94 • n=5 Participants	76.80 Years STANDARD_DEVIATION 5.26 • n=7 Participants	73.93 Years STANDARD_DEVIATION 4.80 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Glasdegib + Azacitidine n=9 Participants 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.	Placebo + Azacitidine n=5 Participants 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.
Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE Treatment emergent AE	7 Participants	4 Participants
Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE Treatment related AE	5 Participants	4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Glasdegib + Azacitidine n=9 Participants 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.	Placebo + Azacitidine n=5 Participants 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.
Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs Treatment emergent SAEs	2 Participants	1 Participants
Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs Treatment related SAEs	1 Participants	1 Participants

Adverse Events

Glasdegib + Azacitidine

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Placebo + Azacitidine

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glasdegib + Azacitidine n=9 participants at risk 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.	Placebo + Azacitidine n=5 participants at risk 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.
Blood and lymphatic system disorders Febrile neutropenia	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	20.0% 1/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Cardiac disorders Cardiopulmonary failure	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Infections and infestations COVID-19 pneumonia	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Glasdegib + Azacitidine n=9 participants at risk 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.	Placebo + Azacitidine n=5 participants at risk 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.
Blood and lymphatic system disorders Anaemia	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Blood and lymphatic system disorders Neutropenia	44.4% 4/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	40.0% 2/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Eye disorders Retinal detachment	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Gastrointestinal disorders Colitis	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Gastrointestinal disorders Colitis ulcerative	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Gastrointestinal disorders Diarrhoea	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Gastrointestinal disorders Inguinal hernia	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Gastrointestinal disorders Vomiting	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
General disorders Oedema peripheral	0.00% 0/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	20.0% 1/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Infections and infestations Corynebacterium bacteraemia	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Infections and infestations Epstein-Barr virus infection reactivation	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Injury, poisoning and procedural complications Fall	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Investigations C-reactive protein increased	11.1% 1/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	0.00% 0/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.
Investigations Platelet count decreased	0.00% 0/9 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.	20.0% 1/5 • From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.