A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia (BRIGHT AML1019)

• ClinicalTrials.gov Identifier: NCT03416179
• Recruitment Status: Completed
• First Posted: January 31, 2018
• Results First Posted: June 25, 2021
• Last Update Posted: April 21, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population).

Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population).

Condition or disease	Intervention/treatment	Phase
Leukemia, Myeloid, Acute	Drug: glasdegib; Drug: daunorubicin + cytarabine; Drug: azacitidine; Drug: Placebo; Drug: cytarabine; Procedure: HSCT	Phase 3

Detailed Description:

Two separate registration trials conducted under one protocol number are proposed to adequately and independently evaluate the addition of glasdegib in intensive and non-intensive chemotherapy populations. Each study will have an experimental treatment arm and a placebo arm. Endpoints are the same for each study except where specifically indicated.

Assignment to the Intensive Study or the Non-Intensive Study will be made by the Investigator based on the 2017 European LeukemiaNet (ELN) recommendations.

Study B1371019 is a randomized (1:1), double-blind, multi-center, placebo controlled study of chemotherapy in combination with glasdegib versus chemotherapy in combination with placebo in adult patients with previously untreated AML.

Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population).

Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 730 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, multi-center, placebo controlled study.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind study.
• Primary Purpose: Treatment
• Official Title: A RANDOMIZED (1:1), DOUBLE-BLIND, MULTI-CENTER, PLACEBO CONTROLLED STUDY EVALUATING INTENSIVE CHEMOTHERAPY WITH OR WITHOUT GLASDEGIB (PF-04449913) OR AZACITIDINE (AZA) WITH OR WITHOUT GLASDEGIB IN PATIENTS WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA
• Actual Study Start Date: April 20, 2018
• Actual Primary Completion Date: June 5, 2020
• Actual Study Completion Date: January 17, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A (Intensive Study); Glasdegib + '7+3' Induction(s)	Drug: glasdegib; Daily Glasdegib (100 mg, PO), beginning on Day 1 and is to continue up to 2 years post randomization. Following consolidation therapy, glasdegib or placebo will be administered daily for up to 2 years after randomization or until they have minimal residual disease (MRD) negative disease, whichever comes first. Daily Glasdegib (100 mg, PO) or matching placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy.; Other Name: PF-04449913; Drug: daunorubicin + cytarabine; '7+3' (cytarabine 100 mg/m2, IV for 7 days by continuous infusion and daunorubicin 60 mg/m2 for 3 days). If a second induction is needed, Investigators may choose either a 5 day cytarabine continuous infusion plus daunorubicin for 2 days ('5+2') or a 7 day cytarabine continuous infusion plus daunorubicin for 3 days ('7+3'); Drug: cytarabine; Consolidation with single agent cytarabine 3 g/m2 IV for adults <60 years and 1 g/m2 for adults 60 years over 3 BID on Days 1, 3, and 5, every 28 days for up to 4 cycles or alternative single agent cytarabine consolidation schedules may be used per local prescribing information.; Procedure: HSCT; If required, and done per standard of care post Induction(s).
Placebo Comparator: Arm B (Intensive Study); Placebo + '7+3' Induction(s)	Drug: daunorubicin + cytarabine; '7+3' (cytarabine 100 mg/m2, IV for 7 days by continuous infusion and daunorubicin 60 mg/m2 for 3 days). If a second induction is needed, Investigators may choose either a 5 day cytarabine continuous infusion plus daunorubicin for 2 days ('5+2') or a 7 day cytarabine continuous infusion plus daunorubicin for 3 days ('7+3'); Drug: Placebo; Matching placebo (PO) given on Day 1 and is to continue up to 2 years post randomization. Following consolidation therapy, placebo will be administered daily for up to 2 years after randomization or until they have MRD negative disease, whichever comes first. Daily placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy.; Drug: cytarabine; Consolidation with single agent cytarabine 3 g/m2 IV for adults <60 years and 1 g/m2 for adults 60 years over 3 BID on Days 1, 3, and 5, every 28 days for up to 4 cycles or alternative single agent cytarabine consolidation schedules may be used per local prescribing information.; Procedure: HSCT; If required, and done per standard of care post Induction(s).
Experimental: Arm A (Non-intensive study); Glasdegib + azacitidine	Drug: azacitidine; Azacitidine (75 mg/m2, SC or IV) daily for 7 days, in 28 day cycles for as long as they do not meet the criteria for disease progression, unacceptable toxicity, consent withdrawal, or death.; Drug: glasdegib; Glasdegib 100 mg PO QD is to be administered by mouth daily beginning on Day 1 of chemotherapy and will continue if subjects demonstrate reasonable evidence of clinical benefit and do not meet the criteria for progression regardless of any delays/modifications in the chemotherapy treatment. Subjects will continue glasdegib until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever comes first.
Placebo Comparator: Arm B (Non-intensive study); Placebo + azacitidine	Drug: azacitidine; Azacitidine (75 mg/m2, SC or IV) daily for 7 days, in 28 day cycles for as long as they do not meet the criteria for disease progression, unacceptable toxicity, consent withdrawal, or death.; Drug: Placebo; Matching placebo (PO) is to be administered by mouth daily beginning on Day 1 of chemotherapy and will continue if subjects demonstrate reasonable evidence of clinical benefit and do not meet the criteria for progression regardless of any delays/modifications in the chemotherapy treatment. Subjects will continue placebo until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever comes first.

Outcome Measures

Primary Outcome Measures :

1. Intensive Study: Overall Survival (OS) [ Time Frame: Baseline up to 25 months ]
   OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
2. Non-intensive Study: Overall Survival (OS) [ Time Frame: Baseline up to 25 months ]
   OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.

Secondary Outcome Measures :

1. Intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Questionnaire [ Time Frame: Post-baseline up to Week 8 ]
   MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). "Fatigue" was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 numeric rating scale (NRS), where 0 = "not present" and 10 = "as bad as you can imagine". Percentage of participants who had improvement in "fatigue" symptoms reported in this outcome measure.
2. Non-intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MDASI-AML/MDS Questionnaire at Week 12 [ Time Frame: Post-baseline up to Week 12 ]
   MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). "Fatigue" was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" and 10 = "as bad as you can imagine". Percentage of participants who had improvement in "fatigue" symptoms reported in this outcome measure.
3. Intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg) [ Time Frame: Day 1 up to maximum of 2 years ]
   Complete remission (CR) was defined based on 2017 European LeukemiaNet (ELN) recommendations. CR: Bone marrow blasts <5 percentage (%); absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) greater than equal to (>=) 1.0*10^9/Liter (L); platelet count >=100*10^9/L. CRMRD-neg: CR with negativity for a genetic marker by reverse transcription quantitative polymerase chain reaction (RT-qPCR), or CR with negativity by Multiparameter Flow Cytometry (MFC).
4. Non-intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg) [ Time Frame: Day 1 up to maximum of 3 years ]
   CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
5. Intensive Study: Percentage of Participants With Complete Remission Including Negative Minimal Residual Disease (CRMRD-neg) [ Time Frame: Day 1 up to maximum of 2 years ]
   CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
6. Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Negative Minimal Residual Disease (CRMRD-neg) [ Time Frame: Day 1 up to maximum of 3 years ]
   CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
7. Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi) [ Time Frame: Day 1 up to maximum of 2 years ]
   CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC less than (<) 1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods.
8. Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi) [ Time Frame: Day 1 up to maximum of 3 years ]
   CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC <1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods.
9. Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS) [ Time Frame: Day 1 up to maximum of 2 years ]
   MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods.
10. Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS) [ Time Frame: Day 1 up to maximum of 3 years ]
    MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods.
11. Intensive Study: Percentage of Participants With Partial Remission (PR) [ Time Frame: Day 1 up to maximum of 2 years ]
    PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L.
12. Non-intensive Study: Percentage of Participants With Partial Remission (PR) [ Time Frame: Day 1 up to maximum of 3 years ]
    PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L.
13. Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) [ Time Frame: Day 1 up to maximum of 3 years ]
    CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
14. Intensive Study: Duration of Response (DoRi) [ Time Frame: From date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause (maximum up to 2 years) ]
    DoRi: only defined for participants who have ever achieved CRi or better (included CR as well) on study as the time from date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause. CRi: not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. Participants last known to be alive who were free from relapse after CRi or better were censored at the date of last disease assessment that verifies their status.
15. Non-intensive Study: Duration of Response (DoRi) or (DoRh) [ Time Frame: From date of first achieving CRi/CRh or better to the date of relapse/disease progression after CRi/CRh or better or death due to any cause (maximum up to 3 years) ]
    DoRi: only defined for participants who have ever achieved CRi or better (included CR and CRh) on study as the time from date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause. DoRh: participants who had ever achieved CRh or better (included CR) on study as the time from date of first achieving CRh or better to the date of disease progression, or relapse after CRh or better, or death due to any cause. CRi: not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
16. Non-intensive Study: Time to Response [ Time Frame: From the date of randomization to the first documentation of response (CRi/CRh or better) (maximum up to 3 years) ]
    TTRi:Participants who achieved CRi or better, as the time from date of randomization to first documentation of response(CRi or better).TTRh:Participants who achieved CRh or better, as the time from date of randomization to first documentation of response(CRh or better). CRi:not qualifying for CR, neutrophil<0.5*10^9/L or platelets<50*10^9, absence of extramedullary disease,absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
17. Intensive Study: Event-free Survival (EFS) [ Time Frame: From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 2 years) ]
    EFS: Time from the date of randomization to the date of treatment failure (TF), relapse from CR, or death from any cause, whichever comes first. TF was defined as failure to achieve CR during the induction cycle (including the re-induction cycle if there is one) and the event date for TF is the day of randomization. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L.
18. Non-intensive Study: Event-free Survival (EFS) [ Time Frame: From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 3 years) ]
    EFS: Time from the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first. TF was defined as failure to achieve CR during the induction cycle (including the re-induction cycle if there is one) and the event date for TF is the day of randomization. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L.
19. Intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score [ Time Frame: Day 1 up to maximum of 2 years ]
    MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). The 13 core symptoms and 6 core interference items had highest frequency and/or severity in participants with various cancers and treatment types. It was measured at severity of symptoms and related interference at their worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" or "did not interfere" and 10 = "worst" or "interfered completely".
20. Non-intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score [ Time Frame: Day 1 up to maximum of 3 years ]
    MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). The 13 core symptoms and 6 core interference items had highest frequency and/or severity in participants with various cancers and treatment types. It was measured at severity of symptoms and related interference at their worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" or "did not interfere" and 10 = "worst" or "interfered completely".
21. Intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score [ Time Frame: Day 1 up to maximum of 2 years ]
    EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), the EuroQoL visual analogue scale (EQ-VAS). EQ-5D: descriptive system measures a participant's health state on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participant is asked to indicate his/her health state by rating each dimension on a 5-level scale (1=no problem, 5=extreme problem). This rating resulted in a 1-digit number expressing the level selected for that dimension. The digits for the 5 dimensions were combined in a 5-digit number describing the respondent's health state. The EQ-5D index scores ranges from 0 to 1, with 0=worst health state and 1=perfect health.
22. Non-intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score [ Time Frame: Day 1 up to maximum of 3 years ]
    EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ-5D: descriptive system measures a participant's health state on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participant is asked to indicate his/her health state by rating each dimension on a 5-level scale (1=no problem, 5=extreme problem). This rating resulted in a 1-digit number expressing the level selected for that dimension. The digits for the 5 dimensions were combined in a 5-digit number describing the respondent's health state. The EQ-5D index scores ranges from 0 to 1, with 0=worst health state and 1=perfect health.
23. Intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS) [ Time Frame: Day 1 up to maximum of 2 years ]
    EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ VAS records the respondent's self-rated health on a 20-cm vertical, VAS from 0 (worst imaginable health state) to 100 (best imaginable health state).
24. Non-intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS) [ Time Frame: Day 1 up to maximum of 3 years ]
    EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ VAS records the respondent's self-rated health on a 20-cm vertical, VAS from 0 (worst imaginable health state) to 100 (best imaginable health state).
25. Intensive Study: Participants Global Impression of Symptoms (PGIS) [ Time Frame: Day 1 up to maximum of 2 years ]
    PGIS: is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time. It uses a 4-point Likert scale as follows: In the last 24 hours, symptoms are: 1-"absent (no symptoms)", 2-"mild", 3-" moderate", 4="severe".
26. Non-intensive Study: Participants Global Impression of Symptoms (PGIS) [ Time Frame: Day 1 up to maximum of 3 years ]
    PGIS: is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time. It uses a 4-point Likert scale as follows: In the last 24 hours, symptoms are: 1-"absent (no symptoms)", 2-"mild", 3-" moderate", 4="severe".
27. Intensive Study: Participants Global Impression of Change (PGIC) [ Time Frame: Day 1 up to maximum of 2 years ]
    PGIC: a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 7-point Likert scale anchored by (1) 'very much improved' to (7) 'very much worse', with (4) =' no change'. The PGIC is a measure of "participant rating of global improvement and satisfaction with treatment".
28. Non-intensive Study: Participants Global Impression of Change (PGIC) [ Time Frame: Day 1 up to maximum of 3 years ]
    PGIC: a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 7-point Likert scale anchored by (1) 'very much improved' to (7) 'very much worse', with (4) =' no change'. The PGIC is a measure of "participant rating of global improvement and satisfaction with treatment".
29. Intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 2 years ]
    AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
30. Non-intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 3 years ]
    AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
31. Intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 2 years ]
    A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
32. Non-intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 3 years ]
    A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
33. Intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 2 years ]
    Hematology laboratory test included: anemia, hemoglobin increased, international normalized ratio (INR) increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
34. Non-intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 3 years ]
    Hematology laboratory test included: anemia, hemoglobin increased, INR increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
35. Intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 2 years ]
    Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, creatine phosphokinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
36. Non-intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 3 years ]
    Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, CPK increased, creatinine increased, GGT increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
37. Intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 2 years ]
    Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
38. Non-intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [ Time Frame: Day 1 up to maximum of 3 years ]
    Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
39. Intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib [ Time Frame: Induction, Day 10+/-1: pre-dose, 1, 4 hour (hr); Consolidation phase, Day 1: pre-dose, 1, 4 hr ]
    Ctrough of Glasdegib was measured in nanogram per milliliter (ng/mL).
40. Non-intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib [ Time Frame: Pre-dose: Cycle 1 Day 15 and Cycle 2 Day 1 ]
    Ctrough of Glasdegib was measured in ng/mL.
41. Intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval [ Time Frame: Day 1 up to maximum of 2 years ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported.
42. Non-intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval [ Time Frame: Day 1 up to maximum of 3 years ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the Intensive and Non Intensive study (unless where indicated):

1. Subjects with untreated AML according to the World Health Organization (WHO) 2016 Classification2, including those with:

   • AML arising from MDS or another antecedent hematologic disease (AHD).
   • AML after previous cytotoxic therapy or radiation (secondary AML).
2. 18 years of age (In Japan, 20 years of age).

3. Adequate Organ Function as defined by the following:

   • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) 3 x upper limit of normal (ULN), excluding subjects with liver function abnormalities due to underlying malignancy.
   • Total serum bilirubin 2 x ULN (except subjects with documented Gilbert's syndrome).
   • Estimated creatinine clearance 30 mL/min as calculated using the standard method for the institution.
4. QTc interval 470 msec using the Fridericia correction (QTcF).

5. All anti cancer treatments (unless specified) should be discontinued 2 weeks from study entry, for example: targeted chemotherapy, radiotherapy, investigational agents, hormones, anagrelide or cytokines.

   • For control of rapidly progressing leukemia, all trans retinoic acid (ATRA), hydroxyurea, and/or leukopheresis may be used before and for up to 1 week after the first dose of glasdegib.
6. Serum or urine pregnancy test (for female subjects of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (hCG) negative at screening.
7. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use at least one highly effective method of contraception throughout the study and for 180 days after the last dose of azacitidine, cytarabine, or daunorubicin; and the last dose of glasdegib or placebo, whichever occurs later.

8. Female subjects of non childbearing potential must meet at least 1 of the following criteria:

   1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
   2. Have medically confirmed ovarian failure; or
   3. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.

   All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.

9. Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
10. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
11. Subjects who are willing and able to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow [BM] assessments).

Exclusion Criteria:

Subjects with any of the following characteristics/conditions will not be included in the study:

1. Acute Promyelocytic Leukemia (APL) and APLwith PML RARA, subjects (WHO 2016 classification).

2. AML with BCR ABL1 or t(9;22)(q34;q11.2) as a sole abnormality.

   • Complex genetics may include t(9;22) cytogenetic translocation.
3. Subjects with known active CNS leukemia.
4. Participation in other clinical studies involving other investigational drug(s) (Phases 1 4) within 4 weeks prior study entry and/or during study participation.
5. Subjects known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a patient who refuses blood product support.
6. Subjects with another active malignancy on treatment with the exception of basal cell carcinoma, non melanoma skin cancer, cervical carcinoma in situ. Other prior or concurrent malignancies will be considered on a case by case basis.
7. Any one of the following ongoing or in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, symptomatic arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms.
8. Subjects with an active, life threatening or clinically significant uncontrolled systemic infection not related to AML.
9. Subjects with left ventricular ejection fraction (LVEF) <50% are excluded from the Intensive Chemotherapy Study only.
10. Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the Intensive Chemotherapy Study only.
11. Known malabsorption syndrome or other condition that may significantly impair absorption of study medication in the investigator's judgment (eg, gastrectomy, lap band, Crohn's disease) and inability or unwillingness to swallow tablets or capsules.
12. Current use or anticipated requirement for drugs that are known strong CYP3A4/5 inducers.
13. Concurrent administration of herbal preparations.
14. Major surgery or radiation within 4 weeks of starting study treatment.

15. Documented or suspected hypersensitivity to any one of the following:

    • For subjects assigned to intensive chemotherapy, documented or suspected hypersensitivity to cytarabine (not including drug fever or exanthema, including known cerebellar side effects) or daunorubicin.
    • For subjects assigned to non intensive chemotherapy, documented or suspected hypersensitivity to azacitidine or mannitol.
16. Known active drug or alcohol abuse.
17. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
18. Pregnant females or breastfeeding female subjects.
19. Known recent or active suicidal ideation or behavior.
20. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.

Contacts and Locations

Locations

United States, California

UCLA Department of Medicine

Los Angeles, California, United States, 90095

UCLA Drug Information/Investigational Drugs

Los Angeles, California, United States, 90095

UCLA Hematology/Oncology Clinic

Los Angeles, California, United States, 90095

UCLA Ronald Reagan Medical Center

Los Angeles, California, United States, 90095

UC Irvine Health - Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868-3201

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94143

University of California, San Francisco

San Francisco, California, United States, 94143

UCLA Hematology/Oncology - Westlake Village

Westlake Village, California, United States, 91361

United States, Georgia

Augusta University Medical Center

Augusta, Georgia, United States, 30912

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States, 30912

United States, Massachusetts

Tufts Medical Center Investigational Drug Pharmacy

Boston, Massachusetts, United States, 02111

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, Missouri

MidAmerica Division, Inc., c/o Research Medical Center

Kansas City, Missouri, United States, 64132

United States, New York

Northwell Health/Monter Cancer Center

Lake Success, New York, United States, 11042

North Shore University Hospital

Manhasset, New York, United States, 11030

Long Island Jewish Medical Center

New Hyde Park, New York, United States, 11040

University of Rochester Medical Center

Rochester, New York, United States, 14642

United States, Ohio

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Oregon

OHSU Center for Health and Healing

Portland, Oregon, United States, 97239

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Tennessee

Centennial Medical Center

Nashville, Tennessee, United States, 37203

TriStar Bone Marrow Transplant

Nashville, Tennessee, United States, 37203

United States, Texas

Baylor University Medical Center

Dallas, Texas, United States, 75246

Blood Cancer and Stem Cell Transplant Clinic

San Antonio, Texas, United States, 78229

Methodist Healthcare System of San Antonio

San Antonio, Texas, United States, 78229

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Swedish Medical Center

Seattle, Washington, United States, 98122

Australia, New South Wales

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia, 2010

St George Hospital

Kogarah, New South Wales, Australia, 2217

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Austria

Landeskrankenhaus Salzburg, Universitatsklinik fur Innere Medizin III der PMU

Salzburg, Austria, 5020

Uniklinikum Salzburg, Landeskrankenhaus Salzburg

Salzburg, Austria, 5020

Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhugel

Wien, Austria, 1130

Belgium

AZ Sint-Jan Brugge-Oostende av

Brugge, Belgium, B-8000

Universitaire Ziekenhuizen Brussel (UZ Brussel)

Brussels, Belgium, B-1090

Universitaire Ziekenhuizen Brussel

Brussels, Belgium, B-1090

Universitaire Ziekenhuizen Leuven

Leuven, Belgium, B-3000

Canada, Manitoba

Health Sciences Centre

Winnipeg, Manitoba, Canada, R3A 1R9

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Ontario

Sunnybrook Research Institute

Toronto, Ontario, Canada, M4N 3M5

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

CIUSSS de l'Est-de-l'Ile-de- Montréal - Hôpital Maisonneuve-Rosemont

Montreal, Quebec, Canada, H1T 2M4

Canada, Saskatchewan

Royal University Hospital

Saskatoon, Saskatchewan, Canada, S7N 0W8

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada, S7N 4H4

China, Anhui

The First Affiliated Hospital of USTC, Anhui Provincial Hospital

Hefei, Anhui, China, 230001

Anhui Provincial Hospital

Hefei, Anhui, China, 230071

China, Fujian

Fujian Medical University Union Hospital

Fuzhou, Fujian, China, 350001

China, Guangdong

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China, 510080

Guangdong Second Provincial General Hospital

Guangzhou, Guangdong, China, 510317

China, Hebei

Hebei Yanda Lu Daopei Hospital

Langfang, Hebei, China, 065201

China, Henan

Henan Provincial People's Hospital/Hematology Department

Zhengzhou, Henan, China, 450003

Henan Cancer Hospital

Zhengzhou, Henan, China, 450008

China, Hubei

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center

Wuhan, Hubei, China, 430030

China, Sichuan

West China Hospital, Sichuan University

Chengdu, Sichuan, China, 610041

China, Tianjin

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin, China, 300020

China, Zhejiang

The First Affiliated Hospital College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310003

China

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, China, 200025

Czechia

Interni hematologicka a onkologicka klinika, Fakultni nemocnice Brno

Brno, Czechia, 625 00

Nemocnicni lekarna

Brno, Czechia, 625 00

Ustavni lekarna

Ostrava - Poruba, Czechia, 708 52

Klinika hematoonkologie

Ostrava-Poruba, Czechia, 708 52

Interní hematologická klinika, Fakultni nemocnice Královské Vinohrady

Praha 10, Czechia, 100 34

Ústavni lékárna

Praha 10, Czechia, 100 34

France

CHU Henri Mondor

Créteil, France, 94010

CHU de Nantes

Nantes cedex 1, France, 44093

CHU de Nantes Hotel Dieu

Nantes cedex, France, 44093

Hopital Saint Louis

Paris, France, 75010

Centre Hospitalier Lyon Sud - Service d'Hematologie

Pierre-Benite cedex, France, 69495

Institut Gustave Roussy

Villejuif cedex, France, 94805

Germany

Klinikum der Universitaet Muenchen

Munich, Bavaria, Germany, 81377

Philipps-Universitaet Marburg

Marburg, Hesse, Germany, 35032

Universitätsklinikum Köln

Koeln, North Rhine Westphalia, Germany, 50937

Universitaetsklinikum Muenster

Muenster, North Rhine-westphalia, Germany, 48149

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, Germany, 20246

Medizinische Hochschule Hannover

Hannover, Germany, 30625

Hungary

Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika, Hematologia Tanszek

Debrecen, Hungary, 4032

Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika

Debrecen, Hungary, 4032

Petz Aladár Megyei Oktató Kórház, II. Belgyógyászat- Hematológiai Osztály

Győr, Hungary, 9024

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvar, Hungary, 7400

Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia

Nyiregyhaza, Hungary, 4400

Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz,

Nyiregyhaza, Hungary, 4400

Israel

Rambam Health Care Campus

Haifa, Israel, 3109601

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Hadassah Medical Center (Ein Kerem)

Jerusalem, Israel, 91120

Hemato-oncology ambulatory Service

Petah Tikva, Israel, 4941492

Rabin Medical Center, Beilinson Hospital

Petah Tikva, Israel, 4941492

Italy

AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi, Clinica Di Ematologia

Torrette Di Ancona, Ancona, Italy, 60126

SOD Farmacia-Dipt dei servizi -AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi

Torette Di Ancona, AN, Italy, 60126

A.O.U. di Ferrara- Arcispedale Sant'Anna,

Cona, Ferrara, FE, Italy, 44124

AO Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro -

Pesaro, PU, Italy, 61122

Azienda Ospedaliera Universitaria Senese.

Siena, SI, Italy, 53100

Azienda Ospedaliero Universitaria di Bologna Policlinico S.Orsola Malpighi

Bologna, Italy, 40138

Azienda Ospedaliera Universitaria Senese

Siena, Italy, 53100

Japan

Japanese Red Cross Nagoya Daini Hospital

Nagoya, Aichi, Japan, 466-8650

University of Fukui Hospital

Yoshida-gun, Fukui, Japan, 910-1193

Gunma University Hospital

Maebashi, Gunma, Japan, 371-8511

Kobe University Hospital

Kobe-shi, Hyogo, Japan, 650-0017

Yokohama City University Medical Center

Yokohama, Kanagawa, Japan, 232-0024

Tohoku University Hospital

Sendai, Miyagi, Japan, 980-8574

Osaka City University Hospital

Osaka-City, Osaka, Japan, 545-8586

Kindai University Hospital

Osaka-Sayama, Osaka, Japan, 589-8511

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan, 411-8777

National Hospital Organization Disaster Medical Center

Tachikawa, Tokyo, Japan, 190-0014

Akita University Hospital

Akita, Japan, 010-8543

Kyushu University Hospital

Fukuoka, Japan, 812-8582

National Hospital Organization Kumamoto Medical Center

Kumamoto, Japan, 860-0008

Nagasaki University Hospital

Nagasaki, Japan, 852-8501

Tokyo Medical University Hospital

Tokyo, Japan, 160-0023

Korea, Republic of

Chonbuk National University Hospital

Jeonju-si, Jeollabuk-do, Korea, Republic of, 54907

Inje University Busan Paik Hospital

Busan, Korea, Republic of, 47392

Keimyung University Dongsan Hospital

Daegu, Korea, Republic of, 42601

Gachon University Gil Medical Center

Incheon, Korea, Republic of, 21565

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Clinical Trial Center, Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Samsung Medical Center

Seoul, Korea, Republic of, 06351

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, Korea, Republic of, 06591

Mexico

Instituto Nacional de Cancerología

México, MÉX, Mexico, 14080

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo LEON, Mexico, 64460

Poland

Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne

Gdansk, Poland, 80-214

WWCOiT im. M. Kopernika w Lodzi

Lodz, Poland, 93-513

Romania

Institutul Oncologic 'Prof. Dr. Ion Chiricuta'

Cluj-Napoca, Cluj, Romania, 400124

Spitalul Clinic Municipal Filantropia Craiova, Sectia Clinica Hematologie

Craiova, Dolj, Romania, 200136

Sp. Clinic de Urgenta Militar Central Dr. Carol Davila

Bucharest, Romania, 010825

Spitalul Clinic Coltea, Clinica de Hematologie

Bucuresti, Romania, 030171

Russian Federation

State Budgetary Healthcare Institution of Moscow

Moscow, Russian Federation, 129301

SBHI NNR NN RCH n. a. N.A. Semashko

Nizhniy Novgorod, Russian Federation, 603126

State Budgetary Institution of Ryazan Region 'Regional Clinical Hospital' (SBI RR RCH)

Ryazan, Russian Federation, 390039

V.A Almazov NMRC

Saint Petersburg, Russian Federation, 197341

Spain

Hospital del Mar

Barcelona, Spain, 08003

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08025

Hospital Universitario Arnau de Vilanova

Lleida, Spain, 25198

Hospital General Universitario Gregorio Maranon

Madrid, Spain, 28007

Hospital Universitario Ramon y Cajal

Madrid, Spain, 28034

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Hospital Universitari i Politecnic La Fe

Valencia, Spain, 46026

Sweden

Universitetssjukhuset Orebro

Orebro, Sweden, 701 85

Karolinska Universitetssjukhuset Huddinge

Stockholm, Sweden, 141 86

Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan, 704

National Taiwan University Hospital

Taipei, Taiwan, 100

Taipei Veterans General Hospital

Taipei, Taiwan, 11217

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan, 112

Chang Gung Memorial Hospital-Linkou Branch

Taoyuan City, Taiwan, 333

United Kingdom

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom, SM2 5PT

University Hospitals Birmingham NHS Foundation Trust

Birmingham, WEST Midlands, United Kingdom, B15 2TH

Imperial College Healthcare NHS Trust

London, United Kingdom, W12 0HS

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] April 12, 2019

Statistical Analysis Plan  [PDF] April 14, 2020

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cortes JE, Dombret H, Merchant A, Tauchi T, DiRienzo CG, Sleight B, Zhang X, Leip EP, Shaik N, Bell T, Chan G, Sekeres MA. Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. Future Oncol. 2019 Nov;15(31):3531-3545. doi: 10.2217/fon-2019-0373. Epub 2019 Sep 13.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03416179
• Other Study ID Numbers: B1371019; 2017-002822-19 ( EudraCT Number ); BRIGHT ( Other Identifier: Alias Study Number ); BRIGHT AML1019 ( Other Identifier: Alias Study Number )
• First Posted: January 31, 2018
• Results First Posted: June 25, 2021
• Last Update Posted: April 21, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

glasdegib; untreated; Hedgehog Inhibitor

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Cytarabine; Azacitidine; Daunorubicin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Enzyme Inhibitors; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors