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

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.

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.

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

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'.

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.

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.

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

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'.

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.

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.

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

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'.

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.

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.

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.

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

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'.

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

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.

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.

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.

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.

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.

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.

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.

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.

Analysis is not final for this outcome measure at primary completion date (PCD), complete data will be posted at study completion date (SCD).

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.

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.

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

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.

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.

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

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.

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.

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.

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 24 hours. Ctrough = Pre-dose concentration, observed directly from data.

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

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.

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.

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

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.

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.

Daunorubicinol was a metabolite of daunorubicin.

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

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

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.

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.

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.

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 patients 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.

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.

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.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD. Safety assessments included number of participants with TEAEs, serious TEAEs, treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0, and with vital signs and laboratory test abnormalities.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

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.

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

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.

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.

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.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

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.

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.

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 patients 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.

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.

Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD. Safety assessments included number of participants with TEAEs, serious TEAEs, treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0, and with vital signs and laboratory test abnormalities.