A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies

Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.

Time frame: Baseline up to maximum 486 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.

Time frame: Baseline up to maximum 343 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.

Time frame: Baseline up to maximum 841 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.

Time frame: For 25 mg: Baseline up to maximum 108 days; For 50 mg: Baseline up to maximum 151 days; For 100 mg: Baseline up to maximum 444 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.

Time frame: Day 1 up to Day 28 of Cycle 1 (28 days)

Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).

Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.

Time frame: Day -3 up to anytime between Day 21 and Day 28 of first induction cycle (24 to 31 days)

Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).

Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.

Time frame: Day 1 up to Day 28 of Cycle 1 (28 days)

Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).

Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.

Time frame: Day -5 up to Day 28 of Cycle 1 (33 days)

Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).

AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.

Time frame: Day 1 up to 28 days after last dose of study drug (maximum up to 514 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.

Time frame: Day 1 up to 28 days after last dose of study drug (maximum up to 371 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.

Time frame: Day 1 up to 28 days after last dose of study drug (maximum up to 869 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE:any untoward medical occurrence at any dose that resulted in death;was life threatening;required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability/incapacity;resulted in congenital anomaly/birth defect. TEAEs:events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE:any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. National cancer institute common terminology criteria (NCI-CTCAE) Grade(G) v4.0:G 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G 4:life-threatening consequence, urgent intervention indicated.

Time frame: Day 1 up to 28 days after last dose of study drug (For 25 mg: maximum up to 136 days; For 50 mg: maximum up to 179 days; For 100 mg: maximum up to 472 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.

Time frame: Baseline up to maximum 514 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, number of participants analyzed signifies participants evaluable for the specific parameter.

Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Participants that had both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.

Time frame: Baseline up to maximum 371 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here number of participants analyzed signifies participants evaluable for the specific parameter.

Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Participants that had both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.

Time frame: Baseline up to maximum 869 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here number of participants analyzed signifies participants evaluable for the specific parameter.

Laboratory parameters included- hematology: lymphocytes/leukocytes percentage (%), neutrophils/leukocytes, basophils/leukocytes, eosinophils/leukocytes and monocytes/leukocytes (%), prothrombin time second (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase units per liter (u/l), protein gram/liter (g/l), blood urea nitrogen (BUN) millimoles per liter (mmol/l), urate, chloride, calcium (mmol/l); urinalysis: specific gravity, pH, urine glucose and ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low, abnormal high or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and high value while on study were reported as 'Abnormal low and Abnormal high'.

Time frame: For 25 mg: Baseline up to maximum 136 days; For 50 mg: Baseline up to maximum 179 days; For 100 mg: Baseline up to maximum 472 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, number of participants analyzed signifies participants evaluable for the specific parameter.

DMR included complete remission (CR), CR with incomplete blood count recovery (Cri), morphologic leukemia-free state (MLFS), marrow CR (mCR) and partial remission (PR). CR: \>=11 gram per deciliter (g/dL) hemoglobin (Hgb), \>=1\*10\^9 neutrophils (L), \>=100\*10\^9 platelets (L), 0% blasts, \<=5% bone marrow blasts (BMB), normal maturation of all cell lines, if had persistent dysplasia. . CRi: \<1000 neutrophils (mcL), \<100000 platelets (mcL), \<5% BMB, either neutrophils or platelets not recovered, no extramedullary disease (EMD). MLFS: 1000 neutrophils (mcL) and \<100000 platelets (mcL), \<5% BMB, neutrophils and platelets not recovered, flow cytometry negative, no EMD. PR: \>=1000 neutrophils (mcL), \>=100000 platelets (mcL), decrease to 5-25 and \>=50% decrease from start, Blasts \<=5% if Auer rod positive. mCR: hematologic improvement (HI) response, \<=5% and decreased by \>=50% BMB. PR: decrease by \>=50% but still \>5% BMB.

Time frame: Baseline up to maximum 736 days

Population: Full analysis set (FAS) included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for participants who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 486 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for participants who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 841 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, Number of participants analyzed signifies participants evaluable for this outcome measure.

Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for participants who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 1408 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Rac was the observed accumulation ratio for AUCtau, determined as ratio of Day 21 AUCtau to Day -5 AUCtau. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

LDAC= low dose ara-cytarabine/low dose cytarabine. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 12 hours.

Time frame: AUCinf: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; AUCtau: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, number of participants analyzed signifies participants evaluable for the specific parameter.

AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: AUCinf: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1; AUCtau: 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Time frame: AUCinf: 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing at Day 1 of Cycle 1 and pre-dose, 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing at 7 of Cycle 1; AUCtau: 0 to 24 hours post azacitidine dosing on Day 1 and 7 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Daunorubicinol was a metabolite of daunorubicin. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

AUCtau was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: 0 to 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: 0 to 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of participants analyzed signifies participants evaluable for the specific timepoint.

AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUClast = area under the curve from time zero to last quantifiable concentration. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Time frame: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Time frame: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Time frame: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of participants analyzed signifies participants evaluable for the specific timepoint.

Ara-uridine was a metabolite of cytarabine. Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 12 hours. Ctrough = Pre-dose concentration, observed directly from data. Ara-uridine was a metabolite of cytarabine.

Time frame: Cmax, Cmin: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Cavg: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Ctrough: Pre-LDAC dosing on Day 2 and Day 10 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax: 0.25, 0.5, 1, 2, 6 hrs post azacitidine dose on Day 1/Cycle 1;Cmin: Pre-dose, 0.25, 0.5, 1, 2, 6 hrs post azacitidine dose on Day 7/Cycle 1;Cavg: 0 to 24 hrs post azacitidine dose on Day 7/Cycle 1;Ctrough:Pre azacitidine dose on Day 7/Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

LDAC= low dose ara-cytarabine/low dose cytarabine. Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours, dosing interval was of 12 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax, Cmin: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Cavg: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Ctrough: Pre-LDAC dose on Day 2 and Day 10 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, number of participants analyzed signifies participants evaluable for the specific timepoint.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax, Cmin: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle (IC) 1; Cavg: 0 to 24 hours post dose on Day 3 of IC 1; Ctrough: Pre-dose on Day 3 of IC 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. Daunorubicinol was a metabolite of daunorubicin.

Time frame: Cmax, Cmin: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle (IC) 1; Cavg: 0 to 24 hours post dose on Day 3 of IC 1; Ctrough: Pre-dose on Day 3 of IC 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax, Cmin: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and 21 of Cycle 1; Cavg: 0 to 24 hours post PF-04449913 dose on Day 10 and 21 of Cycle; Ctrough: Pre-dose on Day 10 and 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax, Cmin: Pre-dose, 0.5, 1, 6, and 24 hrs post dose on Day 3, 10 of induction Cycle (IC) 1 and 4 hrs post dose on Day 10 of IC 1; Cavg: 0 to 24 hrs post dose on Day 3 and Day 10 of IC 1; Ctrough: Pre dose on Day 3 and Day 10 of IC 1 (PF-04449913 Dose)

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax, Cmin: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1; Cavg: 0 to 24 hors post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1; Ctrough: Pre PF-04449913 dosing on Day 7 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants analyzed signifies participants evaluable for the specific timepoint.

Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

Time frame: Cmax, Cmin: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1; Cavg: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day 21 of Cycle 1; Ctrough: Pre-dose on Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here number of participants analyzed signifies participants evaluable for the specific parameter.

Rss = Ratio of Day 21 AUCtau to Day -5 AUCinf. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.

Time frame: AUCtau: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day 21 of Cycle 1; AUCinf: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

LDAC= low dose ara-cytarabine/low dose cytarabine. Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.

Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, number of participants analyzed signifies participants evaluable for the specific parameter.

Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium

Time frame: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of at induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Ara-uridine was a metabolite of cytarabine.

Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Time frame: 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing on Day 1 of Cycle 1 and pre-dose, 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing on Day 7 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

LDAC= low dose ara-cytarabine/low dose cytarabine.

Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Time frame: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Daunorubicinol was a metabolite of daunorubicin.

Time frame: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Time frame: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Time frame: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of Induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of Induction Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Time frame: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants analyzed signifies participants evaluable for the specific timepoint.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for participants with AML- CR: neutrophils \[mcL\] \>=1000, platelets(pt)\[mcL\] \>=10\^5, BMB \<5%. CRi: neutrophils (mcL) \<1000 or pt (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and pt (mcL) \<10\^5, BMB \<5%. PR: neutrophils (mcL) \>=1000, pt (mcL) \>=100000, decrease to 5-25 and \>=50% decrease from start. PRi: neutrophils (mcL) \<1000 or pt (mcL) \<10\^5, BMB decrease to 5-25 and \>=50% decrease from start. Minor Response: BMB \>=25% decrease from start. CRc: neutrophils (mcL) \>1,000, pt (mcL) \>10\^6, BMB \<5%. CRm: neutrophils (mcL) \>1,000, pt (mcL) \>100,000, BMB \<5%. For participants with myelodysplastic syndrome (MDS), DMR- CR: \>=11 Hgb (g/dL), \>=1\*10\^9 neutrophils(L), \>=100\*10\^9 pt(L), 0% blasts, \<=5% BMB. mCR: HI response, \<=5% and decreased by \>=50% BMB. PR: decrease by \>=50% but still \>5% BMB. Only those responses which had at least 1 participant were reported.

Time frame: Day 1 up to end of treatment (maximum up to 486 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, number of participants analyzed signifies participants evaluable for the specified rows.

Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for AML- CR:neutrophils(nt)\[mcL\] \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: nt(mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: nt(mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: nt(mcL) \>=1000, platelets (mcL) \>=100000, decrease to 5-25 and \>=50% decrease from start. PRi: nt(mcL) \<1000 or platelets (mcL) \<100000, BMB decrease to 5-25 and \>=50% decrease from start. Minor Response: BMB \>=25% decrease from start. Cytogenetic CR (CRc): nt(mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. CRm: nt(mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. For participants with myelodysplastic syndrome (MDS), DMR was defined as - CR: \>=11 Hgb (g/dL), \>=1\*10\^9 nt(L), \>=100\*10\^9 platelets (L), 0% blasts, \<=5% BMB. mCR: HI response, \<=5% and decreased by \>=50% BMB. PR: decrease by \>=50% but still \>5% BMB. Only those responses which had at least 1 participant were reported.

Time frame: Day 1 up to end of treatment (maximum up to 343 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for participants with AML- CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, decrease to 5-25 and \>=50% decrease from start. PRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB decrease to 5-25 and \>=50% decrease from start. Minor Response: BMB \>=25% decrease from start. CRc: neutrophils (mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. CRm: neutrophils (mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. Only those responses which had at least 1 participant were reported.

Time frame: Day 1 up to end of treatment (maximum up to 841 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

Best response observed for: CR, Cri, MLFS, PR, PRi, CytogeneticCR(CRc), MolecularCR(CRm). For AML-CR:neutrophils(nt) \[mcL\]\>=1000, platelets(pt)\[mcL\]\>=10\^5, BMB\<5%. CRi:nt(mcL)\<1000/pt(mcL)\<10\^5, BMB\<5%. MLFS:nt(mcL)1000 and pt(mcL)\<10\^5, BMB\<5%. PR:nt(mcL)\>=1000, pt(mcL)\>=10\^5, decrease to 5-25 and \>=50% decrease from start. PRi: nt\<1000, \<10\^5. CRc: nt(mcL)\>1,000, pt(mcL)\>10\^5, BMB\<5%. CRm: nt(mcL)\>1,000, pt(uL)\>10\^5, BMB\<5%. For myelodysplasia-CR: hemoglobin(Hgb)\[gram per deciliter{g/dL}\]\>=11, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, blasts0%, BMB\<=5%. mCR:\<=5% and decreased by \>=50% BMB. PR:decrease by\>=50% with \>5% BMB, CRc: disappearance of chromosomal abnormality, no new appearance, PRc:\>=50% reduced chromosomal abnormality. For myleofibrosis-CR: hgb(g/L)\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, All \<=ULN, BMB \<=5%. PR: hgb\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9. CML- PR: 1-35% Philadelphia chromosome(PC) positive(+) cells, CR:0% PC+ cells. Responses with at least 1 participant were reported.

Time frame: From first dose of study drug up to disease progression (maximum duration of 1408 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

Best response observed for: CR, Cri, MLFS, PR, PRi, CytogeneticCR(CRc), MolecularCR(CRm). For AML-CR:neutrophils(nt) \[mcL\]\>=1000, platelets(pt)\[mcL\]\>=10\^5, BMB\<5%. CRi:nt(mcL)\<1000/pt(mcL)\<10\^5, BMB\<5%. MLFS:nt(mcL)1000 and pt(mcL)\<10\^5, BMB\<5%. PR:nt(mcL)\>=1000, pt(mcL)\>=10\^5, decrease to 5-25 and \>=50% decrease from start. PRi: nt\<1000, \<10\^5. CRc: nt(mcL)\>1,000, pt(mcL)\>10\^5, BMB\<5%. CRm: nt(mcL)\>1,000, pt(uL)\>10\^5, BMB\<5%. For myelodysplasia-CR: hemoglobin(Hgb)\[gram per deciliter{g/dL}\]\>=11, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, blasts0%, BMB\<=5%. mCR:\<=5% and decreased by \>=50% BMB. PR:decrease by\>=50% with \>5% BMB, CRc: disappearance of chromosomal abnormality, no new appearance, PRc:\>=50% reduced chromosomal abnormality. For myleofibrosis-CR: hgb(g/L)\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, All \<=ULN, BMB \<=5%. PR: hgb\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9. CML- PR: 1-35% Philadelphia chromosome(PC) positive(+) cells, CR:0% PC+ cells. Responses with at least 1 participant were reported.

Time frame: Day 1 up to End of Treatment (25 mg: maximum up to 108 days; 50 mg: maximum up to 151 days; 100 mg: maximum up to 444 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, number of participants analyzed signifies participants evaluable for the specified rows.

Vital signs included blood pressure (sitting or supine) and heart rate. Vital sign criteria included: Systolic BP: \<90 millimeter of mercury \[mmHg\]; Systolic BP change from baseline: maximum increase and decrease \>=30 mmHg; Diastolic BP minimum \< 50 mmHg; Diastolic BP change from baseline: maximum decrease and increase \>=20 mmHg; heart rate \<40 and \>120 beats per minute. Clinically significant changes in vital signs were determined by the investigator's discretion.

Time frame: Baseline up to maximum 1146 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, Number of participants analyzed signifies participants evaluable for this outcome measure.

Vital signs included blood pressure (sitting or supine) and heart rate. Vital sign criteria included: Systolic BP: \<90 millimeter of mercury \[mmHg\]; Systolic BP change from baseline: maximum increase and decrease \>=30 mmHg; Diastolic BP minimum \< 50 mmHg; Diastolic BP change from baseline: maximum decrease and increase \>=20 mmHg; heart rate \<40 and \>120 beats per minute. Clinically significant changes in vital signs were determined by the investigator's discretion.

Time frame: Baseline up to maximum 1436 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), blood urea nitrogen (BUN) (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.

Time frame: Baseline up to maximum 1146 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, Number of participants analyzed signifies participants evaluable for this outcome measure.

Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), blood urea nitrogen (BUN) (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.

Time frame: Baseline up to maximum 1436 months

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

AE: any untoward medical occurrence in participant who received study drug or medical device without regard to possibility of causal relationship with the treatment or usage. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.

Time frame: Day 1 up to 28 days after last dose of study drug (Maximum up to 1146 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, Number of participants analyzed signifies participants evaluable for this outcome measure.

AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE:any untoward medical occurrence at any dose that resulted in death,was life threatening,required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability/incapacity,resulted in congenital anomaly/birth defect. TEAEs:events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE:any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. National cancer institute common terminology criteria (NCI-CTCAE) Grade(G) v4.0:G 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G 4:life-threatening consequence, urgent intervention indicated.

Time frame: Day 1 up to 28 days after last dose of study drug (Maximum up to 1436 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Overall survival was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact.

Time frame: First dose of study drug up to death or date of last contact (maximum up to 514 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

Overall survival was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact.

Time frame: First dose of study drug up to death or date of last contact (maximum up to 841 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

OS was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact.

Time frame: First dose of study drug up to death or date of last contact (maximum up to 1408 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 486 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 841 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 1408 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.

Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (mRNA, fresh tissue) at baseline to day 21 cycle 1 is reported.

Time frame: Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21)

Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, number of participants analyzed signifies participants evaluable for the specific parameter.

Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (mRNA, fresh tissue) at baseline to day 21 cycle 1 is reported.

Time frame: Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21)

Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, number of participants analyzed signifies participants evaluable for the specific parameter.

Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (Blood, mRNA) at baseline to day 21 cycle 1 is reported.

Time frame: Baseline, Day 21 of Cycle 1(Predose)

Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, Number of Participants analyzed signifies participants evaluable for the specific parameter.

Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (mRNA, fresh tissue) at baseline to day 21 cycle 1 is reported.

Time frame: Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21)

Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here number of participants analyzed signifies participants evaluable for the specific parameter.

Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (Blood, mRNA) to end of treatment is reported.

Time frame: Baseline, at the end of treatment (hours unspecified, any day maximum up to 841 days)

Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, Number of participants analyzed signifies participants evaluable for the specific parameter.

AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUClast = area under the curve from time zero to last quantifiable concentration. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Time frame: AUCtau: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 of Cycle 1; AUClast and AUCinf: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs.

CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: Pharmacokinetic (PK) parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.

Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1

Population: PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs.

The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 841 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, Number of participants analyzed signifies participants evaluable for this outcome measure.

The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 486 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.

Time frame: Day 1 up to end of treatment (maximum up to 1408 days)

Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.