| Primary | Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy Cohort | 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. | 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). | Posted | | Count of Participants | | Participants | | Day -5 up to Day 28 of Cycle 1 (33 days) | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG002 | Monotherapy Cohort: PF-04449913 100 mg | Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort | 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. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | 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) | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Primary | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Monotherapy Cohort | Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | 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 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | |
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| Primary | Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort | 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'. | 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. | Posted | | Count of Participants | | Participants | | 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 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Primary | Number of Participants With DLTs: Combination Cohort 1 | 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. | 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). | Posted | | Count of Participants | | Participants | | Day 1 up to Day 28 of Cycle 1 (28 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Primary | Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1 | 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. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Day 1 up to 28 days after last dose of study drug (maximum up to 514 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Primary | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 1 | Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 486 days | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Primary | Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1 | 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'. | 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. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 514 days | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Primary | Number of Participants With DLTs: Combination Cohort 2 | 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. | 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). | Posted | | Count of Participants | | Participants | | Day -3 up to anytime between Day 21 and Day 28 of first induction cycle (24 to 31 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Primary | Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2 | 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. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Day 1 up to 28 days after last dose of study drug (maximum up to 371 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Primary | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 2 | Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 343 days | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Primary | Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2 | 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'. | 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. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 371 days | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Primary | Percentage of Participants Achieving Disease Modifying Response (DMR): Expansion Cohort | 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. | Full analysis set (FAS) included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Number | 90% Confidence Interval | Percentage of participants | | Baseline up to maximum 736 days | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Primary | Number of Participants With DLTs: Combination Cohort 3 | 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. | 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). | Posted | | Count of Participants | | Participants | | Day 1 up to Day 28 of Cycle 1 (28 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Primary | Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3 | 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. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Day 1 up to 28 days after last dose of study drug (maximum up to 869 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Primary | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 3 | Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 841 days | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Primary | Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3 | 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'. | 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. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 869 days | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Single Dose- Maximum Observed Plasma Concentration (Cmax) of PF-04449913: Monotherapy Cohort | | Pharmacokinetic (PK) parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | | Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG002 | Monotherapy Cohort: PF-04449913 100 mg | Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Single Dose- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04449913: Monotherapy Cohort | | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG002 | Monotherapy Cohort: PF-04449913 100 mg | Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Single Dose- Terminal Plasma Half-life (T1/2) of PF-04449913: Monotherapy Cohort | Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Mean | Standard Deviation | Hours | | Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1 | | | | ID | Title | Description |
|---|
| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG002 | Monotherapy Cohort: PF-04449913 100 mg |
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| Secondary | Single Dose- Area Under the Plasma Concentration Curve: From Time Zero to End of Dosing Interval (AUCtau), From Time Zero to Last Quantifiable Concentration (AUClast) and From Time Zero to Infinity (AUCinf) of PF-04449913 for Monotherapy Cohort | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg |
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| Secondary | Single Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | | Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1 | | | | ID | Title | Description |
|---|
| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Single Dose- Volume of Distribution (Vz/F) of PF-04449913: Monotherapy Cohort | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liter | | Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG002 |
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| Secondary | Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | |
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| Secondary | Multiple Dose- Tmax of PF-04449913: Monotherapy Cohort | | 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. | Posted | | Median | Full Range | Hours | | Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG002 | Monotherapy Cohort: PF-04449913 100 mg | Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Multiple Dose- AUCtau of PF-04449913: Monotherapy Cohort | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Multiple Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | | Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Multiple Dose- Accumulation Ratio (Rac) of PF-04449913: Monotherapy Cohort | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Ratio | | 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 and Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Multiple Dose- Steady State Accumulation Ratio (Rss) of PF-04449913: Monotherapy Cohort | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Ratio | | 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 | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | |
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| Secondary | Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Monotherapy Cohort | 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. | 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. | Posted | | Mean | Standard Deviation | Ratio | | Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21) | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). | | OG001 | Monotherapy Cohort: PF-04449913 50 mg | Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Number of Participants With Best Response: Monotherapy Cohort | 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. | 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. | Posted | | Count of Participants | | Participants | No | 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) | | | | ID | Title | Description |
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| OG000 | Monotherapy Cohort: PF-04449913 25 mg | Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first). |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- Tmax of PF-04449913: Combination Cohort 1 | | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- AUCtau of PF-04449913: Combination Cohort 1 | AUCtau was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 0 to 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- CL/F of PF-04449913: Combination Cohort 1 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1 | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- Tmax of Cytarabine: Combination Cohort 1 | LDAC= low dose ara-cytarabine/low dose cytarabine. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- T1/2 of Cytarabine: Combination Cohort 1 | 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. | 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. | Posted | | Mean | Standard Deviation | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1 | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- Tmax of Ara-uridine: Combination Cohort 1 | Ara-uridine was a metabolite of cytarabine. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- Tmax of PF-04449913: Combination Cohort 2 | | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- AUCtau of PF-04449913: Combination Cohort 2 | AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- CL/F of PF-04449913: Combination Cohort 2 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- Tmax of Daunorubicin: Combination Cohort 2 | | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- T1/2 of Daunorubicin: Combination Cohort 2 | Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Mean | Standard Deviation | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- AUCinf and AUCtau of Daunorubicin: Combination Cohort 2 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- Tmax of Daunorubicinol: Combination Cohort 2 | Daunorubicinol was a metabolite of daunorubicin. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Multiple Dose- AUCtau of Daunorubicinol: Combination Cohort 2 | Daunorubicinol was a metabolite of daunorubicin. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Combination Cohort 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. | 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. | Posted | | Mean | Standard Deviation | Ratio | | Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Ratio of GLI1 Levels at Baseline to Day 21 Cycle1: Combination Cohort 2 | 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. | 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. | Posted | | Mean | Standard Deviation | Ratio | | Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Number of Participants With Best Response: Combination Cohort 1 | 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. | 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. | Posted | | Count of Participants | | Participants | | Day 1 up to end of treatment (maximum up to 486 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Number of Participants With Best Response: Combination Cohort 2 | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Count of Participants | | Participants | | Day 1 up to end of treatment (maximum up to 343 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m^2 daily IV for first 3 days of Cycle. Participants with <= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles. |
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| Secondary | Percentage of Participants With Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR: Combination Cohort 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Number | 95% Confidence Interval | Percentage of participants | | Day 1 up to end of treatment (maximum up to 486 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 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. | 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. | Posted | | Median | 95% Confidence Interval | Months | | Day 1 up to end of treatment (maximum up to 486 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Time to Response: Combination Cohort 1 | 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. | 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. | Posted | | Median | 95% Confidence Interval | Months | | Day 1 up to end of treatment (maximum up to 486 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Overall Survival: Combination Cohort 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Median | 95% Confidence Interval | Months | | First dose of study drug up to death or date of last contact (maximum up to 514 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first). |
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| Secondary | Overall Survival (OS): Expansion Cohort | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Median | 95% Confidence Interval | Months | | First dose of study drug up to death or date of last contact (maximum up to 1408 days) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With Best Response: Expansion Cohort | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Count of Participants | | Participants | No | From first dose of study drug up to disease progression (maximum duration of 1408 days) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Percentage of Participants With CR/CRi and DMR: Expansion Cohort | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Number | 95% Confidence Interval | Percentage of Participants | | Day 1 up to end of treatment (maximum up to 1408 days) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Duration of Response: Expansion Cohort | 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. | 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. | Posted | | Median | 95% Confidence Interval | Months | | Day 1 up to end of treatment (maximum up to 1408 days) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Time to Response: Expansion Cohort | 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. | 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. | Posted | | Median | 95% Confidence Interval | Months | | Day 1 up to end of treatment (maximum up to 1408 days) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Expansion Cohort | 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. | 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. | Posted | | Mean | Standard Deviation | Ratio | | Baseline, Day 21 of Cycle 1(Predose) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3 | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- Tmax of PF-04449913: Combination Cohort 3 | | 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. | Posted | | Median | Full Range | Hours | | Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- AUCtau of PF-04449913: Combination Cohort 3 | AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 0 to 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- CL/F of PF-04449913: Combination Cohort 3 | 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. | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | | Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- Tmax of Azacitidine: Combination Cohort 3 | | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3 | 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. | PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Overall Survival: Combination Cohort 3 | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Median | 95% Confidence Interval | Months | | First dose of study drug up to death or date of last contact (maximum up to 841 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Ratio of GLI1 Levels at Baseline to End of Treatment: Combination Cohort 3 | 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. | 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. | Posted | | Mean | Standard Deviation | Ratio | | Baseline, at the end of treatment (hours unspecified, any day maximum up to 841 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With Best Response: Combination Cohort 3 | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Count of Participants | | Participants | | Day 1 up to end of treatment (maximum up to 841 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Percentage of Participants With CR/CRi and DMR: Combination Cohort 3 | 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. | FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. | Posted | | Number | 95% Confidence Interval | Percentage of participants | | Day 1 up to end of treatment (maximum up to 841 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3 | 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. | 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. | Posted | | Median | 95% Confidence Interval | Months | | Day 1 up to end of treatment (maximum up to 841 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Time to Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3 | 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. | 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. | Posted | | Median | 95% Confidence Interval | Months | | Day 1 up to end of treatment (maximum up to 841 days) | | | | ID | Title | Description |
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| OG000 | Combination Cohort 3: PF-04449913 100 mg + Azacitidine | Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With Laboratory Test Abnormalities: Continuation Cohort | 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'. | 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. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 1146 days | | | | ID | Title | Description |
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| OG000 | Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg | Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Expansion Cohort | 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. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Day 1 up to 28 days after last dose of study drug (Maximum up to 1436 days) | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With Clinically Significant Vital Signs: Expansion Cohort | 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. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 1436 days | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With Clinically Significant Vital Signs: Continuation Cohort | 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. | 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. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 1146 days | | | | ID | Title | Description |
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| OG000 | Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg | Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Continuation Cohort | 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. | 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. | Posted | | Count of Participants | | Participants | | Day 1 up to 28 days after last dose of study drug (Maximum up to 1146 days) | | | | ID | Title | Description |
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| OG000 | Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg | Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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| Secondary | Number of Participants With Laboratory Test Abnormalities: Expansion Cohort | 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'. | Safety analysis set included all enrolled participants who received at least 1 dose of study medication. | Posted | | Count of Participants | | Participants | | Baseline up to maximum 1436 months | | | | ID | Title | Description |
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| OG000 | Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first). |
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