Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Azacitidine

Daunorubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

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.

glasdegib

'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');

daunorubicin + cytarabine

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.

azacitidine

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.

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.

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.

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.

cytarabine

If required, and done per standard of care post Induction(s).

HSCT

Pfizer CT.gov Call Center

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).

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).

Randomized, double-blind, multi-center, placebo controlled study.

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

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

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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".

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.

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.

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).

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".

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".

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.

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.

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.

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.

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.

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.

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.

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.

Ctrough of Glasdegib was measured in nanogram per milliliter (ng/mL).

Ctrough of Glasdegib was measured in ng/mL.

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.

Pfizer

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. All-Cause Mortality was assessed for all randomized participants whereas serious and other adverse events were assessed for safety population.

Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m\^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m\^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m\^2 IV daily for 5 days and daunorubicin 60 mg/m\^2 IV daily for 2 days. Participants with \<5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m\^2 IV for adults \>=60 to \<60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).

Intensive Study: Glasdegib + Cytarabine + Daunorubicin

Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m\^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m\^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m\^2 IV daily for 5 days and daunorubicin 60 mg/m\^2 IV daily for 2 days. Participants with \<5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m\^2 IV for adults \>=60 to \<60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).

Intensive Study: Placebo + Cytarabine + Daunorubicin

Participants received chemotherapy with azacitidine 75 mg/m\^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).

Non-intensive Study: Glasdegib + Azacitidine

Participants received chemotherapy with azacitidine 75 mg/m\^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).

Non-intensive Study: Placebo + Azacitidine

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Full analysis (FA) set included all randomized participants.

In this study, inadvertently a participant was counted twice for an non-SAE "Pyrexia" at PCD, at SCD update this duplicity has been rectified. Due to this reason total number of participants affected by non-SAE in non-intensive placebo arm was updated to "148".

Pfizer ClinicalTrials.gov Call Center

Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio less than (\<) 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO + Cytarabine 100 mg/m\^2 IV + Daunorubicin 60 mg/m\^2 compared to Placebo + Cytarabine 100 mg/m\^2 IV + Daunorubicin 60 mg/m\^2.

FA set included all randomized participants.

Intensive Study: Overall Survival (OS)

Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio \< 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO QD + Azacitidine compared to Placebo + Azacitidine

Non-intensive Study: Overall Survival (OS)

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

Non-intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MDASI-AML/MDS Questionnaire at Week 12

Intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)

Non-intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)

Intensive Study: Percentage of Participants With Complete Remission Including Negative Minimal Residual Disease (CRMRD-neg)

Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Negative Minimal Residual Disease (CRMRD-neg)

Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)

Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)

Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)

Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)

Intensive Study: Percentage of Participants With Partial Remission (PR)

Non-intensive Study: Percentage of Participants With Partial Remission (PR)

FA set included all randomized participants. This outcome measure was planned to be analyzed only in non-intensive study.

Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, DORi was not collected, analyzed and reported.

Intensive Study: Duration of Response (DoRi)

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, DORi and DoRh was not collected, analyzed and reported.

Non-intensive Study: Duration of Response (DoRi) or (DoRh)

TTRi

TTRh

Non-intensive Study: Time to Response

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EFS was not collected, analyzed and reported.

Intensive Study: Event-free Survival (EFS)

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EFS was not collected, analyzed and reported.

Non-intensive Study: Event-free Survival (EFS)

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, MDASI-AML/MDS was not collected, analyzed and reported.

Intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, MDASI-AML/MDS was not collected, analyzed and reported.

Non-intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-5D-5L was not collected, analyzed and reported.

Intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-5D-5L was not collected, analyzed and reported.

Non-intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-VAS was not collected, analyzed and reported.

Intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-VAS was not collected, analyzed and reported.

Non-intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIS was not collected, analyzed and reported.

Intensive Study: Participants Global Impression of Symptoms (PGIS)

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIS was not collected, analyzed and reported.

Non-intensive Study: Participants Global Impression of Symptoms (PGIS)

The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIC was not collected, analyzed and reported.

Intensive Study: Participants Global Impression of Change (PGIC)

The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIC was not collected, analyzed and reported.

Non-intensive Study: Participants Global Impression of Change (PGIC)

SAEs

Grade 3 or 4 AE

Grade 5 AE

Safety Analysis (SA) set included all participants who received at least one dose of study drug.

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

SA set included all participants who received at least one dose of study drug.

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

Treatment related AEs

Treatment related SAEs

Intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03

Non-intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03

Anemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade)

Anemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Anemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

Anemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

Anemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade)

Hemoglobin increased: Missing (baseline grade) to Grade <=2 (CTCAE grade)

Hemoglobin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Hemoglobin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

INR increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade)

Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade)

Lymphocyte count increased: Missing (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade)

Neutrophil count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade)

Neutrophil count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Neutrophil count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade)

Platelet count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade)

Platelet count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

Platelet count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade)

White blood cell decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade)

White blood cell decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

White blood cell decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

White blood cell decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade)

SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specified rows.

Intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03

Platelet count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Platelet count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

White blood cell decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade)

White blood cell decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

Non-intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03

Alanine aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade)

Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade)

Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade)

Alanine aminotransferase increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade)

SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific rows.

Spots Global Cancer Trial Database for daunorubicin + cytarabine