A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01546038

Collaborator

(none)

255

Enrollment

Locations

Arms

80.2

Actual Duration (Months)

3.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: PF-04449913 Drug: Low dose ARA-C (LDAC) Drug: PF-04449913 Drug: Decitabine Drug: PF-04449913 Drug: Daunorubicin Drug: Cytarabine Drug: PF-04449913 Drug: Daunorubicin Drug: Cytarabine Drug: PF-04449913 Drug: Low dose ARA-C (LDAC)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

255 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE 1B/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-04449913, AN ORAL HEDGEHOG INHIBITOR, IN COMBINATION WITH INTENSIVE CHEMOTHERAPY, LOW DOSE ARA-C OR DECITABINE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA OR HIGH-RISK MYELODYSPLASTIC SYNDROME

Actual Study Start Date :

Jun 27, 2012

Actual Primary Completion Date :

Jan 3, 2017

Actual Study Completion Date :

Mar 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (Phase 1B) PF-04449913 in combination with low dose ARA-C (LDAC)	Drug: PF-04449913 PF-04449913 administered orally and continuously for 28-days. Drug: Low dose ARA-C (LDAC) Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
Experimental: Arm B (Phase 1B) PF-04449913 in combination with Decitabine	Drug: PF-04449913 PF-04449913 administered orally and continuously for 28 days. Drug: Decitabine Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days
Experimental: Arm C (Phase 1B) PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.	Drug: PF-04449913 PF-04449913 administered orally and continuously for 28 days Drug: Daunorubicin Daunorubicin given using 60 mg/m2 for 3-days Drug: Cytarabine Cytarabine 100 mg/m2 on days 1 through 7
Experimental: P2 Fit (Phase 2 Single Arm) PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.	Drug: PF-04449913 PF-04449913 administered orally and continuously for 28 days Drug: Daunorubicin Daunorubicin given using 60 mg/m2 for 3-days Drug: Cytarabine Cytarabine 100 mg/m2 on days 1 through 7
Other: P2 Unfit (Phase 2 Randomized) Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).	Drug: PF-04449913 PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913) Drug: Low dose ARA-C (LDAC) Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.

Outcome Measures

Primary Outcome Measures

Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B [Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started]
A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade >= 3 non-hematologic toxicity, excluding Grade >= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade <= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) < 500/microliter(mcL) or platelet count < 10 *10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of >28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin.
Percentage of Participants With Complete Response (CR) at Phase 2 Fit [4 years]
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Overall Survival (OS) at Phase 2 Unfit [Randomization to Follow-up (4 years)]
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant.

Secondary Outcome Measures

Overall Survival (OS) at Phase 1B [First dose to Follow-up (4 years)]
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Overall Survival (OS) at Phase 2 Fit [First dose to Follow-up (4 years)]
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B [4 years]
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing <5% myeloblasts with either platelets or neutrophils not recovered (platelets <100,000/mcL or neutrophils <1000/mcL).
Percentage of Participants With Complete Response (CR) at Phase 2 Unfit [4 years]
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit [4 years]
AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow<5%myeloblasts with spicules and no blasts with auer rods,neutrophils<1000/mcL and platelets<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start, neutrophils>=1000/mcL, platelets>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start,neutrophils<1000/mcL or platelets<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and molecular-negative).
Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit [4 years]
For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing <5% myeloblasts with platelets <100,000/mcL or neutrophils <1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by >= 50% decrease but still >5%, peripheral blood showing neutrophils >= 1,000/mcL, platelets >= 100,000/mcL and Hgb>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for >8 weeks); marrow complete response (mCR) (bone marrow showing <=5% myeloblasts and decreased by >= 50%), partial cytogenetic response (>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones).
Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21 [Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21]
Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21 [Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21]
Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21 [Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21]
Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1 [Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1]
Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1 [Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1]
AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1 [Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1]
Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10 [Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10]
Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10 [Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10]
AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10 [Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10]
Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10 [Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10]
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported.
Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10 [Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10]
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported.
Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10 [Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10]
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10 [Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10]
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported.
Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2 [Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2]
Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2 [Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2]
AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2 [Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2]
AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 [Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3]
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.
Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 [Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3]
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported.
Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 [Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3]
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported.
AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 [Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3]
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported.
Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10 [Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10]
Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10 [Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10]
Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10 [Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10]
AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10 [Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10]
Number of Participants With Disease-related Gene Mutations at Phase 1B [Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)]
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline [Baseline (Induction Cycle 1/Day -3 pre-dose)]
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3 [Induction Cycle 1/Day 3, 1 Hour Post dose]
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, >=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3.
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10 [Induction Cycle 1/Day 10, 1 Hour Post dose]
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B [Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In [Induction Cycle 1/Lead-in, 1 Hour Post dose]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3 [Induction Cycle 1/Day 3, 1 Hour Post dose]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3.
Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit [Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)]
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3 [Induction Cycle 1/Day 3, 1 Hour Post dose]
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10 [Induction Cycle 1/Day 10, 1 Hour Post dose]
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1 [Consolidation Cycle 1/Day 1, 1 Hour Post dose]
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10 [Consolidation Cycle 1/Day 10, Pre-dose]
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment [End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)]
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit [Baseline (Induction Cycle 1/Day -3 pre-dose)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3 [Induction Cycle 1/Day 3, 1 Hour Post dose]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10 [Induction Cycle 1/Day 10, 1 Hour Post dose]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment [End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1 [Cycle 1/Day 1, 1 Hour Post dose]
Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10 [Cycle 1/Day 10, Pre-dose]
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm.
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit [Baseline (Cycle 1/Day 1 pre-dose)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1 [Cycle 1/Day 1, 1 Hour Post-dose]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment [End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3 [Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose]
Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene.
Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment [Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)]
Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2.
Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment [Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)]
Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit [Baseline (Induction Cycle 1/Day -3 pre-dose)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2).
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit [Baseline (Cycle 1/Day 1 pre-dose)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1.
Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit [Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported.
Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit [Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose]
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1.
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B [1 year]
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit [1 year]
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality) [4 years]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related) [4 years]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B [4 years]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality) [4 years]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related) [4 years]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit [4 years]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated.
Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML)
For a diagnosis of AML, a bone marrow blast count of 20% or more is required.
For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts
Adequate Organ Function
ECOG Performance Status 0, 1, or 2

Exclusion Criteria:

AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation.
Patients with known active uncontrolled central nervous system (CNS) leukemia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249-6909
3	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
4	UC San Diego Moores Cancer Center - Investigational Drug Services	La Jolla	California	United States	92037-0845
5	UC San Diego Medical Center - La Jolla	La Jolla	California	United States	92037
6	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093-0698
7	Keck Hospital of USC	Los Angeles	California	United States	90033
8	LAC & USC Medical Center	Los Angeles	California	United States	90033
9	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California	United States	90033
10	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
11	Ronald Reagan UCLA Medical Center Drug Information Center	Los Angeles	California	United States	90095
12	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
13	UCLA Drug lnformation/lnvestigational Drugs	Los Angeles	California	United States	90095
14	UCLA Hematology/Oncology Clinic	Los Angeles	California	United States	90095
15	UC San Diego Medical Center - Hillcrest	San Diego	California	United States	92103
16	University of Colorado Denver	Aurora	Colorado	United States	80045
17	University of Colorado Hospital	Aurora	Colorado	United States	80045
18	H.Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
19	Emory University Hospital	Atlanta	Georgia	United States	30322
20	Investigational Drug Service, Emory University Clinic	Atlanta	Georgia	United States	30322
21	The Emory Clinic	Atlanta	Georgia	United States	30322
22	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
23	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
24	Northwestern Medicine Developmental Therapeutics Institute	Chicago	Illinois	United States	60611
25	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
26	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
27	The University of Chicago's Medical Center	Chicago	Illinois	United States	60637
28	University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
29	University of Kansas Hospital	Kansas City	Kansas	United States	66160
30	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas	United States	66205
31	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287
32	Tufts Medical Center	Boston	Massachusetts	United States	02111
33	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
34	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
35	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts	United States	02215
36	University of Michigan Comprehensive Cancer Center Clinical Trials Office	Ann Arbor	Michigan	United States	48109-2800
37	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
38	Siteman Cancer Center - West County	Creve Coeur	Missouri	United States	63141
39	Barnes Jewish Hospital North Campus	Saint Louis	Missouri	United States	63110
40	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
41	Washington University School of Medicine - Division of Bone Marrow Transplant & Leukemia	Saint Louis	Missouri	United States	63110
42	Washington University School of Medicine, Siteman Cancer Center	Saint Louis	Missouri	United States	63110
43	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
44	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
45	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
46	Cleveland Clinic Cancer Institute	Cleveland	Ohio	United States	44195
47	Centennial Medical Center	Nashville	Tennessee	United States	37203
48	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
49	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
50	The University of Texas, MD Anderson Cancer Center	Houston	Texas	United States	77030
51	University of Washington-Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
52	University of Washington Medical Center	Seattle	Washington	United States	98195
53	Juravinski Cancer Centre @ Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
54	Centre de Sante et de Services Sociaux (CSSS) Champlain - Charles-Le Moyne	Greenfield Park	Quebec	Canada	J4V 2H1
55	Universitaetsklinikum Ulm	Ulm	Baden-wuerttemberg	Germany	89081
56	Johann Wolfgang Goethe University	Frankfurt am Main	Hessen	Germany	60590
57	Medizinische Hochschule Hannover	Hannover	Lower Saxony	Germany	30625
58	Charite -Universitatsmedizin Berlin - Campus Benjamin Franklin	Berlin		Germany	12203
59	Charite - Universitatsmedizin Berlin	Berlin		Germany	13353
60	Universitaetsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
61	Universitaetsklinikum Schleswig-Holstein	Kiel		Germany	24105
62	Universitaetsklinikum Magdeburg A.oe.R.	Magdeburg		Germany	39120
63	Johannes Gutenberg-Universitaet Mainz	Mainz		Germany	55131
64	Universitaetsklinikum Muenster	Muenster		Germany	48149
65	Universitaetsklinikum Ulm	Ulm		Germany	89081
66	Policlinico S. Orsola-Malpighi	Bologna	Province OF Bologna	Italy	40138
67	ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
68	Policlinico Universitario "Umberto I" Universita degli Studi "La Sapienza" Sezione di Ematologia	Rome		Italy	00161
69	A.O. Citta della Salute e della Scienza di Torino - S.C. Ematologia	Torino		Italy	10126
70	Azienda Sanitaria Universitaria Integrata di Udine	Udine		Italy	33100
71	Uniwersyteckie Centrum Kliniczne Gdanskiego Uniwersytetu Medycznego	Gdansk	Pomorskie	Poland	80-952
72	Oddzial Hematologii Z pododzialem chemioterapii-Klinika Hematologii Wojewodzkie Wielospecjalistyczne	Lodz		Poland	93-513
73	Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku	Wroclaw		Poland	53-439
74	Hospital Universitario Virgen del Rocio	Sevilla	Andalucia	Spain	41013
75	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
76	Hospital del Mar	Barcelona		Spain	08003
77	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
78	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
79	Hospital Clinic de Barcelona	Barcelona		Spain	08036
80	Hospital Ramon y Cajal	Madrid		Spain	28034
81	Hospital Universitario y Politecnico La Fe	Valencia		Spain	46026

Sponsors and Collaborators

Pfizer

Investigators

Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01546038

Other Study ID Numbers:

B1371003
2012-000684-24

First Posted:

Mar 7, 2012

Last Update Posted:

Mar 3, 2020

Last Verified:

Feb 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Pfizer

Hedgehog Inhibitor

Acute Myeloid Leukemia

Myelodysplastic syndrome

Intensive chemotherapy

LDAC

glasdegib

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Cytarabine

Decitabine

Daunorubicin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Phase 1B:Unfit(unfit for intensive chemotherapy)participants with prior decitabine or azacitidine for high risk MDS or AHD(antecedent hematologic disease)were eligible for the LDAC arm only;with prior cytarabine were eligible for decitabine arm only.Phase 2:Participant's treatment arm assignment was based on the fit or unfit status at screening.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
Period Title: Overall Study
STARTED	17	6	4	3	16	6	71	88	44
Received Treatment	17	6	4	3	16	6	69	84	41
COMPLETED	1	0	0	0	6	2	18	4	1
NOT COMPLETED	16	6	4	3	10	4	53	84	43

Baseline Characteristics

Arm/Group Title	Phase 1B: Glasdegib + LDAC	Phase 1B: Glasdegib + Decitabine	Phase 1B: Glasdegib + Cytarabine/Daunorubicin	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone	Total
Arm/Group Description	Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.	Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.	Total of all reporting groups
Overall Participants	23	7	22	71	88	44	255
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	75.8 (6.5)	75.0 (4.4)	54.9 (12.7)	61.9 (9.6)	76.2 (6.2)	74.5 (4.9)	66.8 (13.9)
Sex: Female, Male (Count of Participants)
Female	8 34.8%	2 28.6%	10 45.5%	28 39.4%	19 21.6%	18 40.9%	85 33.3%
Male	15 65.2%	5 71.4%	12 54.5%	43 60.6%	69 78.4%	26 59.1%	170 66.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
Description	A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade >= 3 non-hematologic toxicity, excluding Grade >= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade <= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) < 500/microliter(mcL) or platelet count < 10 *10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of >28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin.
Time Frame	Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started

Outcome Measure Data

Analysis Population Description
Per protocol analysis set: all enrolled participants in the dose escalation component who received at least 1 dose of glasdegib and of the co-administered chemotherapeutics and who did not have major treatment deviations during the DLT monitoring period.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	3	5	4	2	6	6
Number [Participants]	0 0%	0 0%	0 0%	0 0%	1 1.1%	0 0%

2. Primary Outcome

Title	Percentage of Participants With Complete Response (CR) at Phase 2 Fit
Description	For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	69
Total participants	42.0 182.6%
Participants >= 55 years old	36.7 159.6%
Participants < 55 years old	77.8 338.3%

3. Primary Outcome

Title	Overall Survival (OS) at Phase 2 Unfit
Description	OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant.
Time Frame	Randomization to Follow-up (4 years)

Outcome Measure Data

Analysis Population Description
Full analysis set: all randomized participants of Phase 2 Unfit arm.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	88	44
Median (80% Confidence Interval) [Months]	8.8	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 1B: Glasdegib 100 mg + LDAC, Phase 1B: Glasdegib 200 mg + LDAC
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0020
	Comments	1-sided p-value from the log-rank test stratified by prognosis stratum according to Interactive Voice Response System (IVRS).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.569
	Confidence Interval	(2-Sided) 80% 0.441 to 0.734
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the Cox proportional hazards model stratified by prognosis stratum according to IVRS.

4. Secondary Outcome

Title	Overall Survival (OS) at Phase 1B
Description	OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Time Frame	First dose to Follow-up (4 years)

Outcome Measure Data

Analysis Population Description
Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.

Arm/Group Title	Phase 1B: Glasdegib + LDAC	Phase 1B: Glasdegib + Decitabine	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.	Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	23	7	22
Median (80% Confidence Interval) [Months]	4.4	11.5	37.8

5. Secondary Outcome

Title	Overall Survival (OS) at Phase 2 Fit
Description	OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Time Frame	First dose to Follow-up (4 years)

Outcome Measure Data

Analysis Population Description
Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	69
Total participants	14.9
Participants >= 55 years old	14.7
Participants < 55 years old	NA

6. Secondary Outcome

Title	Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
Description	For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing <5% myeloblasts with either platelets or neutrophils not recovered (platelets <100,000/mcL or neutrophils <1000/mcL).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.

Arm/Group Title	Phase 1B: Glasdegib + LDAC	Phase 1B: Glasdegib + Decitabine	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.	Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	23	7	22
Number (80% Confidence Interval) [Percentage of participants]	8.7 37.8%	28.6 408.6%	54.5 247.7%

7. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
Description	For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Full analysis set: all randomized participants of Phase 2 Unfit arm.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	88	44
Number (80% Confidence Interval) [Percentage of participants]	18.2 79.1%	2.3 32.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 1B: Glasdegib 100 mg + LDAC, Phase 1B: Glasdegib 200 mg + LDAC
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0112
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.2755
	Confidence Interval	(2-Sided) 80% 1.3057 to 13.9994
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the Cox proportional hazards model stratified by prognosis stratum according to IVRS.

8. Secondary Outcome

Title	Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
Description	AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow<5%myeloblasts with spicules and no blasts with auer rods,neutrophils<1000/mcL and platelets<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start, neutrophils>=1000/mcL, platelets>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start,neutrophils<1000/mcL or platelets<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and molecular-negative).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
AML participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	64	78	38
CRi	10.9 47.4%	5.1 72.9%	2.6 11.8%
MLFS	7.8 33.9%	2.6 37.1%	0.0 0%
PR	1.6 7%	6.4 91.4%	2.6 11.8%
PRi	1.6 7%	1.3 18.6%	0.0 0%
MR	10.9 47.4%	6.4 91.4%	10.5 47.7%
SD	6.3 27.4%	16.7 238.6%	21.1 95.9%
CRc	35.9 156.1%	11.5 164.3%	0.0 0%
CRm	37.5 163%	16.7 238.6%	2.6 11.8%

9. Secondary Outcome

Title	Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
Description	For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing <5% myeloblasts with platelets <100,000/mcL or neutrophils <1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by >= 50% decrease but still >5%, peripheral blood showing neutrophils >= 1,000/mcL, platelets >= 100,000/mcL and Hgb>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for >8 weeks); marrow complete response (mCR) (bone marrow showing <=5% myeloblasts and decreased by >= 50%), partial cytogenetic response (>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
MDS participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	5	10	6
mCR	0.0 0%	10.0 142.9%	0.0 0%
PR	0.0 0%	0.0 0%	0.0 0%
SD	0.0 0%	0.0 0%	33.3 151.4%
CRi	20.0 87%	10.0 142.9%	0.0 0%
Unconfirmed SD	0.0 0%	10.0 142.9%	0.0 0%
Unconfirmed CRi	0.0 0%	10.0 142.9%	0.0 0%
mCR (CRi not included)	0.0 0%	10.0 142.9%	0.0 0%
CRc	60.0 260.9%	10.0 142.9%	0.0 0%

10. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Description
Time Frame	Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
Cycle 1/Day 10	1074 (63)	1942 (75)
Cycle 1/Day 21	1242 (56)	2577 (104)

11. Secondary Outcome

Title	Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Description
Time Frame	Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
Cycle 1/Day 10	1.75	4.00
Cycle 1/Day 21	1.34	4.00

12. Secondary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Description
Time Frame	Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
Cycle 1/Day 10	15020 (49)	28600 (17)
Cycle 1/Day 21	16660 (43)	31400 (119)

13. Secondary Outcome

Title	Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Description
Time Frame	Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Measure Participants	4	3
Cycle 1/Day 10	1718 (28)	2381 (28)
Cycle 2/Day 1	1826 (44)	NA (NA)

14. Secondary Outcome

Title	Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Description
Time Frame	Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Measure Participants	4	3
Cycle 1/Day 10	2.00	2.05
Cycle 2/Day 1	1.03	NA

15. Secondary Outcome

Title	AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Description
Time Frame	Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Measure Participants	4	3
Cycle 1/Day 10	NA (NA)	28380 (11)
Cycle 2/Day 1	17060 (29)	NA (NA)

16. Secondary Outcome

Title	Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Description
Time Frame	Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	16	6
Induction Cycle 1/Day 3	674.2 (45)	1622 (25)
Induction Cycle 1/Day 10	1135 (43)	2371 (43)

17. Secondary Outcome

Title	Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Description
Time Frame	Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	16	6
Induction Cycle 1/Day 3	5.99	6.00
Induction Cycle 1/Day 10	4.08	1.04

18. Secondary Outcome

Title	AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Description
Time Frame	Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	16	6
Induction Cycle 1/Day 3	9332 (56)	22840 (43)
Induction Cycle 1/Day 10	16300 (46)	26370 (39)

19. Secondary Outcome

Title	Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Description	Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
LDAC Cycle 1/Day 2	58.50 (58)	100.1 (29)
LDAC Cycle 1/Day 10	63.01 (88)	132.5 (39)
Ara-U Cycle 1/Day 2	379.5 (34)	569.7 (29)
Ara-U Cycle 1/Day 10	452.2 (36)	652.0 (27)

20. Secondary Outcome

Title	Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Description	Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
LDAC Cycle 1/Day 2	0.250	0.250
LDAC Cycle 1/Day 10	0.325	0.250
Ara-U Cycle 1/Day 2	3.97	4.00
Ara-U Cycle 1/Day 10	2.00	1.99

21. Secondary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Description
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
LDAC Cycle 1/Day 2	71.10 (28)	89.35 (28)
LDAC Cycle 1/Day 10	92.28 (25)	143.9 (24)

22. Secondary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Description	Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	17	6
LDAC Cycle 1/Day 2	62.55 (41)	87.49 (29)
LDAC Cycle 1/Day 10	65.56 (76)	134.8 (26)
Ara-U Cycle 1/Day 2	2036 (36)	3050 (29)
Ara-U Cycle 1/Day 10	2283 (43)	3528 (29)

23. Secondary Outcome

Title	Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Description
Time Frame	Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2

Outcome Measure Data

Analysis Population Description
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	4	3
Cycle 1/Day 1	113.4 (59)	174.2 (113)
Cycle 1/Day 2	127.9 (43)	121.7 (37)

24. Secondary Outcome

Title	Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Description
Time Frame	Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	4	3
Cycle 1/Day 1	0.75	0.53
Cycle 1/Day 2	0.58	0.53

25. Secondary Outcome

Title	AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Description
Time Frame	Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Measure Participants	4	3
Cycle 1/Day 1	133.4 (71)	251.5 (140)
Cycle 1/Day 2	NA (NA)	NA (NA)

26. Secondary Outcome

Title	AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Description	Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.
Time Frame	Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	9	2
Cytarabine	1070 (211)	NA (NA)
Ara-U	28420 (32)	NA (NA)

27. Secondary Outcome

Title	Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Description	Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported.
Time Frame	Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3

Outcome Measure Data

Analysis Population Description
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	15	6
Daunorubicin	275.3 (153)	341.0 (82)
Daunorubicinol	195.4 (139)	233.4 (46)

28. Secondary Outcome

Title	Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Description	Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported.
Time Frame	Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	15	6
Daunorubicin	0.500	0.492
Daunorubicinol	1.00	0.642

29. Secondary Outcome

Title	AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Description	Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported.
Time Frame	Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3

Outcome Measure Data

Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	16	6
Daunorubicin	499.3 (61)	424.9 (38)
Daunorubicinol	2152 (24)	2712 (33)

30. Secondary Outcome

Title	Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
Description
Time Frame	Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	42
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	308.7 (74)

31. Secondary Outcome

Title	Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Description
Time Frame	Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Measure Participants	41
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1252 (44)

32. Secondary Outcome

Title	Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Description
Time Frame	Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Measure Participants	41
Median (Full Range) [Hours]	1.67

33. Secondary Outcome

Title	AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Description
Time Frame	Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10

Outcome Measure Data

Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Measure Participants	37
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	17210 (54)

34. Secondary Outcome

Title	Number of Participants With Disease-related Gene Mutations at Phase 1B
Description	Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Time Frame	Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)

Outcome Measure Data

Analysis Population Description
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib; responders and non-responders in each arm with at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + LDAC (Biomarker, Responder)	Phase 1B: Glasdegib + LDAC (Biomarker, Non-Responder)	Phase 1B: Glasdegib + Decitabine (Biomarker,Responder)	Phase 1B: Glasdegib + Decitabine (Biomaker,Non-Responder)	Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder)	Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Arm/Group Description	AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.	AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.	AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Measure Participants	0	9	0	1	11	1
CEBPA (CCAAT/enhancer-binding protein alpha)	3 13%	0 0%	2 9.1%	0 0%
DNMT3A (DNA [cytosine-5]-methyltransferase 3A)	2 8.7%	0 0%	0 0%	0 0%
FLT3 (Fms-like tyrosine kinase 3)	1 4.3%	0 0%	2 9.1%	0 0%
FLT3-ITD (FLT3 internal tandem duplications)	0 0%	0 0%	1 4.5%	0 0%
IDH1 (Isocitrate dehydrogenase 1)	1 4.3%	0 0%	0 0%	0 0%
IDH2 (Isocitrate dehydrogenase 2)	0 0%	0 0%	2 9.1%	0 0%
KIT(Tyrosine-protein kinase Kit)	0 0%	1 14.3%	0 0%	0 0%
KRAS(Kirsten rat sarcoma 2 viral oncogene homolog)	1 4.3%	0 0%	0 0%	0 0%
NPM1 (Nucleophosmin)	0 0%	0 0%	4 18.2%	0 0%
NRAS(Neuroblastoma RAS viral oncogene homolog)	5 21.7%	0 0%	1 4.5%	0 0%
RUNX1 (Runt related transcription factor 1)	1 4.3%	0 0%	1 4.5%	0 0%
TET2 (Tet methylcytosine dioxygenase 2)	3 13%	0 0%	1 4.5%	0 0%
WT1 (Wilm's tumour tumor suppressor gene1)	0 0%	0 0%	0 0%	0 0%

35. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
Description	Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose)

Outcome Measure Data

Analysis Population Description
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	22
MMP-3 (Matrix metalloproteinase-3)	10200
IL-8 (Interleukin-8)	10.7
BDNF (Brain-derived neurotrophic factor)	1200
IL-5 (Interleukin-5)	0.00
VEGF (Vascular endothelial growth factor)	88.00
MCP-1 (Monocyte chemotactic protein-1)	180.5
ITAC:Interferon-inducible T-cell α chemoattractant	0.00

36. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
Description	Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, >=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3.
Time Frame	Induction Cycle 1/Day 3, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	21
Median (Full Range) [pg/mL]	20000

37. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
Description	Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Time Frame	Induction Cycle 1/Day 10, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	21
IL-8	37.00
BDNF	200
IL-5	99.00
VEGF	51.00
MCP-1	684.00
ITAC	0.00

38. Secondary Outcome

Title	Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm.
Time Frame	Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder)	Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.	AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Measure Participants	14	8
Median (Full Range) [pg/mL]	2275.00	3275.00

39. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in.
Time Frame	Induction Cycle 1/Lead-in, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder)	Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.	AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Measure Participants	14	8
Median (Full Range) [ng/mL]	8.90	10.50

40. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3.
Time Frame	Induction Cycle 1/Day 3, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder)	Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.	AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Measure Participants	13	8
Median (Full Range) [pg/mL]	2510.00	3260.00

41. Secondary Outcome

Title	Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
Description	Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit and Unfit portion who received at least 1 dose of glasdegib; responders and non-responders in each arm with at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker,Non-Responder)	Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder)	Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)	Phase 2 Unfit: LDAC Alone (Biomarker, Responder)	Phase 2 Unfit: LDAC Alone (Biomarker, Non-Responder)
Arm/Group Description	AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	32	18	21	40	1	26
CEBPA	6 26.1%	3 42.9%	3 13.6%	5 7%	0 0%	3 6.8%
DNMT3A	12 52.2%	6 85.7%	2 9.1%	13 18.3%	0 0%	6 13.6%
FLT3	3 13%	2 28.6%	1 4.5%	4 5.6%	0 0%	0 0%
FLT3-ITD	2 8.7%	1 14.3%	1 4.5%	2 2.8%	0 0%	2 4.5%
IDH1	2 8.7%	1 14.3%	5 22.7%	5 7%	0 0%	2 4.5%
IDH2	5 21.7%	4 57.1%	2 9.1%	10 14.1%	0 0%	5 11.4%
KIT	2 8.7%	1 14.3%	1 4.5%	2 2.8%	0 0%	1 2.3%
KRAS	0 0%	1 14.3%	0 0%	2 2.8%	0 0%	2 4.5%
NPM1	12 52.2%	3 42.9%	2 9.1%	3 4.2%	0 0%	1 2.3%
NRAS	5 21.7%	1 14.3%	1 4.5%	4 5.6%	0 0%	3 6.8%
RUNX1	7 30.4%	7 100%	10 45.5%	18 25.4%	0 0%	7 15.9%
TET2	7 30.4%	5 71.4%	7 31.8%	8 11.3%	1 1.1%	8 18.2%
WT1	0 0%	1 14.3%	1 4.5%	2 2.8%	0 0%	1 2.3%

42. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
Description	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame	Induction Cycle 1/Day 3, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	57
Factor VII(activated blood coagulation factor VII)	318000
BDNF	700
MMP-3	21000
IL-8	28.00
ITAC	14.00

43. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
Description	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame	Induction Cycle 1/Day 10, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	62
IL-1β (Interleukin-1β)	8.50
IL-6	17.00
Factor VII	292500
BDNF	300
VEGF	69.00
MCP-1	594.00
MMP-3	12000
IL-8	55.00
IL-5	85.00
ITAC	0.00

44. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
Description	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame	Consolidation Cycle 1/Day 1, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	24
MIP-1β (Macrophage Inflammatory Protein-1β)	226.00
BDNF	7000
VEGF	232.50
IL-8	9.90
ITAC	41.50

45. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
Description	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame	Consolidation Cycle 1/Day 10, Pre-dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	20
MIP-1β	239.50
MCP-1	581.00
MMP-3	12000
IL-8	11.00
ITAC	4.10

46. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
Description	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame	End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	42
MIP-1β	338.00
VEGF	133.00
MCP-1	277.00

47. Secondary Outcome

Title	Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	43	22
Median (Full Range) [pg/mL]	323.00	362.00

48. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	Induction Cycle 1/Day 3, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	37	20
Mean (Full Range) [pg/mL]	3.20	10.90

49. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	Induction Cycle 1/Day 10, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	42	20
Mean (Full Range) [pg/mL]	1.20	6.60

50. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	27	15
IL-1β	9.70	6.70
IL-15 (Interleukin-15)	700	600

51. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
Description	Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.
Time Frame	Cycle 1/Day 1, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Measure Participants	18
Median (Full Range) [pg/mL]	483.00

52. Secondary Outcome

Title	Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
Description	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm.
Time Frame	Cycle 1/Day 10, Pre-dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	66	24
BDNF	500	200
ITAC	7.5	0.00

53. Secondary Outcome

Title	Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	Baseline (Cycle 1/Day 1 pre-dose)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder)	Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	28	44
BDNF	2000	900
ICAM-1 (Intercellular cell adhesion molecule-1)	128000	161000
6CKINE	223.50	318.00
BAFF (B-cell activating factor)	704.50	1295.00
MIP-3β	275.00	414.50
Eotaxin-1 (C-C motif chemokine 11)	169.00	0.00

54. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	Cycle 1/Day 1, 1 Hour Post-dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder)	Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	6	12
Factor VII:activated blood coagulation factor VII	311500	234500
IL-6 (Interleukin-6)	0.00	6.80

55. Secondary Outcome

Title	Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame	End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder)	Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	17	18
Median (Full Range) [pg/mL]	0.00	9.40

56. Secondary Outcome

Title	Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
Description	Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene.
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	62
CDKN1A	2.40
SMO	4.80
PTCH2	0.60
MYCN	0.20

57. Secondary Outcome

Title	Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
Description	Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2.
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Measure Participants	62
CCND2	0.80
MSI2	0.80
PTCH2	0.70

58. Secondary Outcome

Title	Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
Description	Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.
Time Frame	Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)

Outcome Measure Data

Analysis Population Description
PD analysis set:all enrolled participants in Phase 2 Unfit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC
Arm/Group Description	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Measure Participants	47
CCND2	0.70
SMO	0.40
CCND1	0.40

59. Secondary Outcome

Title	Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2).
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	39	22
Median (Full Range) [Normalized expression units]	10.9	14.80

60. Secondary Outcome

Title	Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1.
Time Frame	Baseline (Cycle 1/Day 1 pre-dose)

Outcome Measure Data

Analysis Population Description
PD analysis set:all enrolled participants in Phase 2 Unfit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder)	Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	33	55
FOXM1	0.20	0.40
PTCH1	0.20	0.10

61. Secondary Outcome

Title	Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported.
Time Frame	Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Fit (Biomarker, Responder)	Phase 2 Fit (Biomarker, Non-Responder)
Arm/Group Description	AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	45	26
CCNE1	0.60	1.10
MSI2	0.90	0.50

62. Secondary Outcome

Title	Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Description	Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1.
Time Frame	Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose

Outcome Measure Data

Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.

Arm/Group Title	Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder)	Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Arm/Group Description	AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).	AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Measure Participants	33	55
Median (Full Range) [ratio]	1.60	0.50

63. Secondary Outcome

Title	Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
Description	Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description
QTc analysis set: all participants enrolled in the study having at least 1 ECG assessment after receiving at least 1 dose of glasdegib.

Arm/Group Title	Phase 1B: Glasdegib + LDAC	Phase 1B: Glasdegib + Decitabine	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.	Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	21	7	22
QTcF interval increase < 30 msec	16 69.6%	2 28.6%	14 63.6%
QTcF interval increase: 30 to < 60 msec	5 21.7%	3 42.9%	6 27.3%
QTcF interval increase >= 60 msec	0 0%	2 28.6%	2 9.1%
Maximum QTcF interval < 450 msec	10 43.5%	4 57.1%	10 45.5%
Maximum QTcF interval: 450 to < 480 msec	11 47.8%	2 28.6%	10 45.5%
Maximum QTcF interval: 480 to < 500 msec	0 0%	0 0%	1 4.5%
Maximum QTcF interval >= 500 msec	0 0%	1 14.3%	1 4.5%

64. Secondary Outcome

Title	Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
Description	Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description
QTc analysis set: all participants enrolled in the study having at least 1 ECG assessment after receiving at least 1 dose of glasdegib.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	68	83	17
QTcF interval increase < 30 msec	41 178.3%	60 857.1%	12 54.5%
QTcF interval increase: 30 to < 60 msec	21 91.3%	19 271.4%	4 18.2%
QTcF interval increase >= 60 msec	6 26.1%	4 57.1%	1 4.5%
Maximum QTcF interval < 450 msec	46 200%	46 657.1%	8 36.4%
Maximum QTcF interval: 450 to < 480 msec	18 78.3%	29 414.3%	4 18.2%
Maximum QTcF interval: 480 to < 500 msec	3 13%	3 42.9%	3 13.6%
Maximum QTcF interval >= 500 msec	1 4.3%	5 71.4%	2 9.1%

65. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.

Arm/Group Title	Phase 1B: Glasdegib + LDAC	Phase 1B: Glasdegib + Decitabine	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.	Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	23	7	22
Grade 1 AEs	1 4.3%	1 14.3%	0 0%
Grade 2 AEs	2 8.7%	0 0%	3 13.6%
Grade 3 AEs	3 13%	1 14.3%	8 36.4%
Grade 4 AEs	10 43.5%	4 57.1%	10 45.5%
Grade 5 AEs	7 30.4%	1 14.3%	1 4.5%
Missing or unknown AEs	0 0%	0 0%	0 0%

66. Secondary Outcome

Title	Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.

Arm/Group Title	Phase 1B: Glasdegib + LDAC	Phase 1B: Glasdegib + Decitabine	Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Arm/Group Description	Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.	Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.	Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Measure Participants	23	7	22
Grade 1 AEs	3 13%	2 28.6%	2 9.1%
Grade 2 AEs	2 8.7%	0 0%	7 31.8%
Grade 3 AEs	7 30.4%	0 0%	3 13.6%
Grade 4 AEs	6 26.1%	4 57.1%	10 45.5%
Grade 5 AEs	3 13%	0 0%	0 0%
Missing or unknown AEs	0 0%	0 0%	0 0%

67. Secondary Outcome

Title	Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC	Phase 1B: Glasdegib 200 mg + LDAC	Phase 1B: Glasdegib 100 mg + Decitabine	Phase 1B: Glasdegib 200 mg + Decitabine	Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.	Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.	Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Measure Participants	17	6	4	3	16	6
AEs	17 73.9%	6 85.7%	4 18.2%	3 4.2%	16 18.2%	6 13.6%
SAEs	13 56.5%	5 71.4%	4 18.2%	2 2.8%	10 11.4%	3 6.8%

68. Secondary Outcome

Title	Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	69	84	41
Grade 1 AEs	0 0%	2 28.6%	0 0%
Grade 2 AEs	1 4.3%	4 57.1%	1 4.5%
Grade 3 AEs	11 47.8%	15 214.3%	8 36.4%
Grade 4 AEs	52 226.1%	39 557.1%	15 68.2%
Grade 5 AEs	5 21.7%	24 342.9%	17 77.3%
Missing or unknown AEs	0 0%	0 0%	0 0%

69. Secondary Outcome

Title	Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	69	84	41
Grade 1 AEs	0 0%	4 57.1%	4 18.2%
Grade 2 AEs	4 17.4%	9 128.6%	6 27.3%
Grade 3 AEs	15 65.2%	20 285.7%	3 13.6%
Grade 4 AEs	46 200%	34 485.7%	10 45.5%
Grade 5 AEs	1 4.3%	1 14.3%	1 4.5%
Missing or unknown AEs	0 0%	0 0%	0 0%

70. Secondary Outcome

Title	Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.

Arm/Group Title	Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin	Phase 2 Unfit: Glasdegib 100 mg + LDAC	Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.	Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.	Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Measure Participants	69	84	41
AEs	69 300%	84 1200%	41 186.4%
SAEs	35 152.2%	68 971.4%	32 145.5%

Adverse Events

	Phase 1B: Glasdegib 100 mg + LDAC		Phase 1B: Glasdegib 200 mg + LDAC		Phase 1B: Glasdegib 100 mg + Decitabine		Phase 1B: Glasdegib 200 mg + Decitabine		Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin		Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 2 Unfit: Glasdegib 100 mg + LDAC		Phase 2 Unfit: LDAC Alone
Time Frame	4 years
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. All-cause mortality reflects the number of deaths from start of treatment to and including 28 days after last dose. Safety analysis set was evaluated.

Arm/Group Title	Phase 1B: Glasdegib 100 mg + LDAC		Phase 1B: Glasdegib 200 mg + LDAC		Phase 1B: Glasdegib 100 mg + Decitabine		Phase 1B: Glasdegib 200 mg + Decitabine		Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin		Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 2 Unfit: Glasdegib 100 mg + LDAC		Phase 2 Unfit: LDAC Alone
Arm/Group Description	Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.		Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.		Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.		Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.		Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.		Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.		Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.		Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.		Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/17 (35.3%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		5/69 (7.2%)		26/84 (31%)		17/41 (41.5%)
Serious Adverse Events
	Phase 1B: Glasdegib 100 mg + LDAC		Phase 1B: Glasdegib 200 mg + LDAC		Phase 1B: Glasdegib 100 mg + Decitabine		Phase 1B: Glasdegib 200 mg + Decitabine		Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin		Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 2 Unfit: Glasdegib 100 mg + LDAC		Phase 2 Unfit: LDAC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/17 (76.5%)		5/6 (83.3%)		4/4 (100%)		2/3 (66.7%)		10/16 (62.5%)		3/6 (50%)		35/69 (50.7%)		68/84 (81%)		32/41 (78%)
Blood and lymphatic system disorders
Febrile neutropenia	3/17 (17.6%)		3/6 (50%)		0/4 (0%)		1/3 (33.3%)		1/16 (6.3%)		1/6 (16.7%)		14/69 (20.3%)		24/84 (28.6%)		7/41 (17.1%)
Neutropenia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		2/69 (2.9%)		0/84 (0%)		0/41 (0%)
Pancytopenia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		2/41 (4.9%)
Anaemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		6/84 (7.1%)		0/41 (0%)
Disseminated intravascular coagulation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Granulocytopenia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Leukocytosis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Lymphadenitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Thrombocytosis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Cardiac disorders
Acute myocardial infarction	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		1/41 (2.4%)
Cardiac failure congestive	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Angina pectoris	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Atrial fibrillation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Cardiac arrest	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		0/41 (0%)
Cardiac failure	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		0/41 (0%)
Cardiogenic shock	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Myocardial infarction	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		1/41 (2.4%)
Tachyarrhythmia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Ventricular fibrillation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Myocarditis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Tachycardia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Eye disorders
Mydriasis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		0/41 (0%)
Impaired gastric emptying	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Nausea	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Neutropenic colitis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Vomiting	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Abdominal pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		2/69 (2.9%)		0/84 (0%)		0/41 (0%)
Upper gastrointestinal haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Diarrhoea	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		1/41 (2.4%)
Colitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Constipation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Gastrooesophageal reflux disease	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Haematemesis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Lower gastrointestinal haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Pancreatitis acute	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Retroperitoneal haematoma	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
General disorders
Disease progression	3/17 (17.6%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		2/69 (2.9%)		10/84 (11.9%)		5/41 (12.2%)
Fatigue	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		3/84 (3.6%)		0/41 (0%)
Multiple organ dysfunction syndrome	1/17 (5.9%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Nodule	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pyrexia	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		3/84 (3.6%)		1/41 (2.4%)
Asthenia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Death	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
General physical health deterioration	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Mucosal inflammation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Oedema	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Sudden death	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		0/41 (0%)
Hepatobiliary disorders
Cholecystitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		2/69 (2.9%)		0/84 (0%)		0/41 (0%)
Infections and infestations
Appendicitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Bacteraemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		2/69 (2.9%)		1/84 (1.2%)		0/41 (0%)
Cellulitis	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Clostridium difficile infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Enterobacter sepsis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Enterocolitis infectious	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Lower respiratory tract infection bacterial	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Neutropenic sepsis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pneumonia	2/17 (11.8%)		0/6 (0%)		2/4 (50%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		19/84 (22.6%)		7/41 (17.1%)
Sepsis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		6/69 (8.7%)		3/84 (3.6%)		5/41 (12.2%)
Skin infection	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Staphylococcal bacteraemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Septic shock	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		2/84 (2.4%)		1/41 (2.4%)
Abscess	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Aspergillus infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Clostridium difficile colitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		1/84 (1.2%)		0/41 (0%)
Cystitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Device related infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Escherichia urinary tract infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Herpes zoster	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Infected dermal cyst	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Influenza	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Lung infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Otitis media chronic	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Pneumonia fungal	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Pseudomembranous colitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Respiratory tract infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Septic encephalopathy	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Urogenital infection bacterial	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Adenovirus infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Arthritis bacterial	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Mycobacterium avium complex infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Pharyngitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Pneumocystis jirovecii pneumonia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Pseudomonal sepsis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Tooth abscess	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Abdominal infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Clostridial sepsis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Injury, poisoning and procedural complications
Fall	0/17 (0%)		2/6 (33.3%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		0/41 (0%)
Skin abrasion	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Infusion related reaction	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		1/84 (1.2%)		0/41 (0%)
Subdural haematoma	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		2/69 (2.9%)		0/84 (0%)		0/41 (0%)
Femur fracture	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Subarachnoid haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Splenic rupture	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Thoracic vertebral fracture	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Investigations
Lumbar puncture abnormal	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Alanine aminotransferase increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Aspartate aminotransferase increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Laboratory test abnormal	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Metabolism and nutrition disorders
Dehydration	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Gout	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Hyperuricaemia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hyponatraemia	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		2/84 (2.4%)		0/41 (0%)
Tumour lysis syndrome	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Decreased appetite	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Myalgia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Back pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		1/84 (1.2%)		0/41 (0%)
Muscle spasms	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Muscular weakness	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		0/41 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Nervous system disorders
Autonomic nervous system imbalance	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Dizziness	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Ischaemic stroke	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Neurotoxicity	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Polyneuropathy	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Subarachnoid haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Dyskinesia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Presyncope	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		1/84 (1.2%)		0/41 (0%)
Syncope	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		4/84 (4.8%)		0/41 (0%)
Cerebral haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Haemorrhage intracranial	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		3/84 (3.6%)		1/41 (2.4%)
Peripheral sensorimotor neuropathy	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Transient ischaemic attack	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Cerebrovascular accident	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Psychiatric disorders
Bipolar II disorder	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Mental status changes	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Confusional state	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Renal and urinary disorders
Acute kidney injury	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		3/84 (3.6%)		0/41 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Respiratory failure	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pleuritic pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Pneumonitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Cough	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Dyspnoea	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Pleural effusion	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		1/41 (2.4%)
Pulmonary embolism	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Respiratory arrest	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		1/41 (2.4%)
Respiratory distress	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Skin and subcutaneous tissue disorders
Rash generalised	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Rash maculo-papular	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Rash	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Skin toxicity	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Vascular disorders
Hypotension	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		1/69 (1.4%)		0/84 (0%)		0/41 (0%)
Haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Hypertension	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Phase 1B: Glasdegib 100 mg + LDAC		Phase 1B: Glasdegib 200 mg + LDAC		Phase 1B: Glasdegib 100 mg + Decitabine		Phase 1B: Glasdegib 200 mg + Decitabine		Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin		Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin		Phase 2 Unfit: Glasdegib 100 mg + LDAC		Phase 2 Unfit: LDAC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/17 (94.1%)		6/6 (100%)		4/4 (100%)		3/3 (100%)		16/16 (100%)		6/6 (100%)		69/69 (100%)		82/84 (97.6%)		39/41 (95.1%)
Blood and lymphatic system disorders
Anaemia	3/17 (17.6%)		1/6 (16.7%)		2/4 (50%)		1/3 (33.3%)		4/16 (25%)		1/6 (16.7%)		28/69 (40.6%)		37/84 (44%)		17/41 (41.5%)
Febrile neutropenia	3/17 (17.6%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		8/16 (50%)		2/6 (33.3%)		38/69 (55.1%)		8/84 (9.5%)		4/41 (9.8%)
Leukocytosis	1/17 (5.9%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		6/84 (7.1%)		2/41 (4.9%)
Leukopenia	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		9/69 (13%)		0/84 (0%)		0/41 (0%)
Lymphadenitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Neutropenia	7/17 (41.2%)		0/6 (0%)		2/4 (50%)		2/3 (66.7%)		4/16 (25%)		1/6 (16.7%)		15/69 (21.7%)		13/84 (15.5%)		8/41 (19.5%)
Spleen disorder	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Splenomegaly	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Thrombocytopenia	6/17 (35.3%)		1/6 (16.7%)		2/4 (50%)		1/3 (33.3%)		3/16 (18.8%)		2/6 (33.3%)		23/69 (33.3%)		26/84 (31%)		11/41 (26.8%)
Lymphadenopathy	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Cardiac disorders
Angina pectoris	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Atrial fibrillation	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		5/69 (7.2%)		7/84 (8.3%)		1/41 (2.4%)
Diastolic dysfunction	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Palpitations	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Sinus bradycardia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Sinus tachycardia	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		7/69 (10.1%)		0/84 (0%)		0/41 (0%)
Tachycardia	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		1/6 (16.7%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Ventricular tachycardia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pericardial effusion	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Endocrine disorders
Adrenal insufficiency	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hypothyroidism	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Eye disorders
Diplopia	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Eye haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Ocular hyperaemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Photophobia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Scleral pigmentation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Vision blurred	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Abdominal distension	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		10/69 (14.5%)		0/84 (0%)		0/41 (0%)
Abdominal pain	4/17 (23.5%)		0/6 (0%)		1/4 (25%)		1/3 (33.3%)		6/16 (37.5%)		0/6 (0%)		20/69 (29%)		15/84 (17.9%)		4/41 (9.8%)
Abdominal pain upper	2/17 (11.8%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		7/84 (8.3%)		1/41 (2.4%)
Anal fissure	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Anal haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Angina bullosa haemorrhagica	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Ascites	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Constipation	7/17 (41.2%)		3/6 (50%)		2/4 (50%)		1/3 (33.3%)		10/16 (62.5%)		3/6 (50%)		32/69 (46.4%)		21/84 (25%)		6/41 (14.6%)
Diarrhoea	8/17 (47.1%)		2/6 (33.3%)		2/4 (50%)		0/3 (0%)		10/16 (62.5%)		6/6 (100%)		49/69 (71%)		24/84 (28.6%)		9/41 (22%)
Diverticulum	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Dry mouth	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		2/16 (12.5%)		1/6 (16.7%)		10/69 (14.5%)		0/84 (0%)		0/41 (0%)
Dyspepsia	0/17 (0%)		0/6 (0%)		2/4 (50%)		0/3 (0%)		4/16 (25%)		1/6 (16.7%)		12/69 (17.4%)		0/84 (0%)		0/41 (0%)
Dysphagia	1/17 (5.9%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Faeces discoloured	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Flatulence	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Gastritis	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Gastrooesophageal reflux disease	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		2/6 (33.3%)		6/69 (8.7%)		0/84 (0%)		0/41 (0%)
Gingival bleeding	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Gingival pain	0/17 (0%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Haematemesis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Haematochezia	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Haemorrhoidal haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Haemorrhoids	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		4/16 (25%)		2/6 (33.3%)		5/69 (7.2%)		7/84 (8.3%)		0/41 (0%)
Hiatus hernia	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Megacolon	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Mouth haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		5/69 (7.2%)		2/84 (2.4%)		4/41 (9.8%)
Nausea	6/17 (35.3%)		4/6 (66.7%)		4/4 (100%)		1/3 (33.3%)		14/16 (87.5%)		3/6 (50%)		40/69 (58%)		30/84 (35.7%)		5/41 (12.2%)
Oral disorder	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Oral mucosal blistering	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Oral pain	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pancreatitis	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Proctalgia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Retching	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Stomatitis	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		2/3 (66.7%)		5/16 (31.3%)		0/6 (0%)		17/69 (24.6%)		0/84 (0%)		0/41 (0%)
Tongue disorder	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Tooth loss	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Toothache	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Vomiting	1/17 (5.9%)		2/6 (33.3%)		1/4 (25%)		1/3 (33.3%)		5/16 (31.3%)		4/6 (66.7%)		25/69 (36.2%)		18/84 (21.4%)		4/41 (9.8%)
Mouth ulceration	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		3/41 (7.3%)
General disorders
Asthenia	3/17 (17.6%)		1/6 (16.7%)		1/4 (25%)		2/3 (66.7%)		1/16 (6.3%)		0/6 (0%)		8/69 (11.6%)		10/84 (11.9%)		8/41 (19.5%)
Catheter site pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Catheter site swelling	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Chest discomfort	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Chest pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		2/6 (33.3%)		9/69 (13%)		9/84 (10.7%)		1/41 (2.4%)
Chills	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		1/3 (33.3%)		5/16 (31.3%)		0/6 (0%)		21/69 (30.4%)		5/84 (6%)		1/41 (2.4%)
Fatigue	6/17 (35.3%)		1/6 (16.7%)		1/4 (25%)		2/3 (66.7%)		6/16 (37.5%)		2/6 (33.3%)		25/69 (36.2%)		26/84 (31%)		8/41 (19.5%)
Gait disturbance	0/17 (0%)		2/6 (33.3%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Generalised oedema	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hernia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Influenza like illness	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Injection site pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Localised oedema	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Mucosal inflammation	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		8/69 (11.6%)		6/84 (7.1%)		2/41 (4.9%)
Nodule	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Non-cardiac chest pain	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		3/16 (18.8%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Oedema	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		6/69 (8.7%)		0/84 (0%)		0/41 (0%)
Oedema peripheral	5/17 (29.4%)		1/6 (16.7%)		0/4 (0%)		1/3 (33.3%)		7/16 (43.8%)		2/6 (33.3%)		22/69 (31.9%)		22/84 (26.2%)		7/41 (17.1%)
Pain	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		0/6 (0%)		6/69 (8.7%)		4/84 (4.8%)		3/41 (7.3%)
Performance status decreased	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pyrexia	5/17 (29.4%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		10/16 (62.5%)		1/6 (16.7%)		34/69 (49.3%)		23/84 (27.4%)		9/41 (22%)
Thirst	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Catheter site erythema	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		6/69 (8.7%)		0/84 (0%)		0/41 (0%)
Catheter site haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Hepatobiliary disorders
Cholelithiasis	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hyperbilirubinaemia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Immune system disorders
Hypersensitivity	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Infections and infestations
Arthritis bacterial	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Bacteraemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Bronchiolitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Candida infection	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Cellulitis	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Clostridium difficile colitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Clostridium difficile infection	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Device related infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Enterobacter bacteraemia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Enterocolitis bacterial	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Enterocolitis infectious	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Folliculitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Fungal infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Genital infection viral	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Nasopharyngitis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Onychomycosis	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Otitis media	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pneumonia	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		6/69 (8.7%)		9/84 (10.7%)		3/41 (7.3%)
Pneumonia fungal	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		2/6 (33.3%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Pulmonary mycosis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Sepsis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Skin infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Staphylococcal bacteraemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Staphylococcal infection	2/17 (11.8%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Subcutaneous abscess	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Upper respiratory tract infection	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Urinary tract infection	0/17 (0%)		0/6 (0%)		1/4 (25%)		1/3 (33.3%)		0/16 (0%)		1/6 (16.7%)		8/69 (11.6%)		5/84 (6%)		5/41 (12.2%)
Viral infection	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Oral herpes	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		3/84 (3.6%)		3/41 (7.3%)
Injury, poisoning and procedural complications
Contusion	1/17 (5.9%)		2/6 (33.3%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		6/69 (8.7%)		5/84 (6%)		2/41 (4.9%)
Fall	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		9/84 (10.7%)		1/41 (2.4%)
Infusion related reaction	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Post procedural haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Procedural headache	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Skin abrasion	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Vascular access complication	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Investigations
Alanine aminotransferase increased	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		4/16 (25%)		1/6 (16.7%)		21/69 (30.4%)		0/84 (0%)		0/41 (0%)
Amylase increased	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Aspartate aminotransferase increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		17/69 (24.6%)		6/84 (7.1%)		1/41 (2.4%)
Blood alkaline phosphatase increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		13/69 (18.8%)		0/84 (0%)		0/41 (0%)
Blood bilirubin increased	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		19/69 (27.5%)		0/84 (0%)		0/41 (0%)
Blood creatinine increased	2/17 (11.8%)		2/6 (33.3%)		1/4 (25%)		1/3 (33.3%)		0/16 (0%)		1/6 (16.7%)		14/69 (20.3%)		9/84 (10.7%)		3/41 (7.3%)
Blood fibrinogen decreased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Blood uric acid increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Chest X-ray abnormal	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Eastern Cooperative Oncology Group performance status worsened	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Electrocardiogram QT prolonged	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		7/69 (10.1%)		7/84 (8.3%)		1/41 (2.4%)
International normalised ratio increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		7/69 (10.1%)		3/84 (3.6%)		5/41 (12.2%)
Karnofsky scale worsened	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Lipase increased	0/17 (0%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Liver function test increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Lymphocyte count decreased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		0/6 (0%)		6/69 (8.7%)		0/84 (0%)		0/41 (0%)
Neutrophil count decreased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		12/69 (17.4%)		11/84 (13.1%)		1/41 (2.4%)
Platelet count decreased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		18/69 (26.1%)		14/84 (16.7%)		4/41 (9.8%)
Weight decreased	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		9/69 (13%)		17/84 (20.2%)		1/41 (2.4%)
White blood cell count decreased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		4/16 (25%)		0/6 (0%)		20/69 (29%)		13/84 (15.5%)		2/41 (4.9%)
Activated partial thromboplastin time prolonged	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Weight increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
C-reactive protein increased	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		6/84 (7.1%)		6/41 (14.6%)
Metabolism and nutrition disorders
Decreased appetite	1/17 (5.9%)		2/6 (33.3%)		1/4 (25%)		2/3 (66.7%)		2/16 (12.5%)		2/6 (33.3%)		26/69 (37.7%)		29/84 (34.5%)		5/41 (12.2%)
Dehydration	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		6/69 (8.7%)		0/84 (0%)		0/41 (0%)
Gout	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		5/84 (6%)		2/41 (4.9%)
Hyperkalaemia	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		6/69 (8.7%)		0/84 (0%)		0/41 (0%)
Hypermagnesaemia	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Hypernatraemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Hyperphosphataemia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		2/16 (12.5%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hyperuricaemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		0/69 (0%)		7/84 (8.3%)		1/41 (2.4%)
Hypoalbuminaemia	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		2/6 (33.3%)		18/69 (26.1%)		0/84 (0%)		0/41 (0%)
Hypocalcaemia	2/17 (11.8%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		5/16 (31.3%)		2/6 (33.3%)		22/69 (31.9%)		5/84 (6%)		1/41 (2.4%)
Hypoglycaemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hypokalaemia	2/17 (11.8%)		3/6 (50%)		1/4 (25%)		0/3 (0%)		6/16 (37.5%)		2/6 (33.3%)		37/69 (53.6%)		13/84 (15.5%)		6/41 (14.6%)
Hypomagnesaemia	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		4/16 (25%)		2/6 (33.3%)		20/69 (29%)		8/84 (9.5%)		2/41 (4.9%)
Hyponatraemia	2/17 (11.8%)		0/6 (0%)		1/4 (25%)		1/3 (33.3%)		5/16 (31.3%)		1/6 (16.7%)		23/69 (33.3%)		10/84 (11.9%)		0/41 (0%)
Hypophagia	1/17 (5.9%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hypophosphataemia	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		3/16 (18.8%)		0/6 (0%)		15/69 (21.7%)		0/84 (0%)		0/41 (0%)
Hypovolaemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Metabolic acidosis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Tumour lysis syndrome	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Vitamin D deficiency	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hyperglycaemia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		13/69 (18.8%)		0/84 (0%)		0/41 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/17 (5.9%)		2/6 (33.3%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		11/69 (15.9%)		10/84 (11.9%)		0/41 (0%)
Back pain	2/17 (11.8%)		1/6 (16.7%)		2/4 (50%)		2/3 (66.7%)		4/16 (25%)		1/6 (16.7%)		12/69 (17.4%)		9/84 (10.7%)		3/41 (7.3%)
Bone pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		4/16 (25%)		0/6 (0%)		0/69 (0%)		2/84 (2.4%)		3/41 (7.3%)
Joint effusion	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Muscle spasms	5/17 (29.4%)		1/6 (16.7%)		0/4 (0%)		2/3 (66.7%)		10/16 (62.5%)		2/6 (33.3%)		11/69 (15.9%)		19/84 (22.6%)		2/41 (4.9%)
Muscular weakness	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		6/84 (7.1%)		0/41 (0%)
Musculoskeletal pain	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		0/6 (0%)		7/69 (10.1%)		0/84 (0%)		0/41 (0%)
Musculoskeletal stiffness	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Myalgia	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		1/6 (16.7%)		5/69 (7.2%)		5/84 (6%)		0/41 (0%)
Neck pain	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Osteoarthritis	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pain in extremity	1/17 (5.9%)		0/6 (0%)		1/4 (25%)		1/3 (33.3%)		4/16 (25%)		3/6 (50%)		9/69 (13%)		15/84 (17.9%)		2/41 (4.9%)
Pain in jaw	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Periarthritis	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Plantar fasciitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Spinal pain	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Nervous system disorders
Ageusia	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Amnesia	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Central nervous system lesion	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Cognitive disorder	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Dizziness	1/17 (5.9%)		2/6 (33.3%)		1/4 (25%)		1/3 (33.3%)		1/16 (6.3%)		2/6 (33.3%)		12/69 (17.4%)		18/84 (21.4%)		4/41 (9.8%)
Dysgeusia	4/17 (23.5%)		4/6 (66.7%)		1/4 (25%)		1/3 (33.3%)		7/16 (43.8%)		1/6 (16.7%)		19/69 (27.5%)		21/84 (25%)		1/41 (2.4%)
Headache	3/17 (17.6%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		9/16 (56.3%)		2/6 (33.3%)		22/69 (31.9%)		11/84 (13.1%)		5/41 (12.2%)
Lethargy	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Memory impairment	0/17 (0%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Mental impairment	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Paraesthesia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Peroneal nerve palsy	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Presyncope	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Sedation	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Syncope	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hypoaesthesia	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Psychiatric disorders
Agitation	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		3/84 (3.6%)		3/41 (7.3%)
Anxiety	1/17 (5.9%)		2/6 (33.3%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		1/6 (16.7%)		15/69 (21.7%)		3/84 (3.6%)		4/41 (9.8%)
Apathy	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Confusional state	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		7/84 (8.3%)		0/41 (0%)
Depressed mood	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Depression	2/17 (11.8%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		2/6 (33.3%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Disorientation	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Insomnia	1/17 (5.9%)		0/6 (0%)		2/4 (50%)		0/3 (0%)		5/16 (31.3%)		0/6 (0%)		19/69 (27.5%)		10/84 (11.9%)		2/41 (4.9%)
Panic attack	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Delirium	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Hallucination	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Renal and urinary disorders
Acute kidney injury	2/17 (11.8%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		3/16 (18.8%)		2/6 (33.3%)		8/69 (11.6%)		7/84 (8.3%)		1/41 (2.4%)
Dysuria	1/17 (5.9%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Haematuria	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Pollakiuria	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Proteinuria	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Renal cyst	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Renal failure	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Urinary retention	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Urinary incontinence	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		7/84 (8.3%)		0/41 (0%)
Reproductive system and breast disorders
Pelvic pain	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Vaginal haemorrhage	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Vulvovaginal pruritus	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Cough	4/17 (23.5%)		1/6 (16.7%)		1/4 (25%)		1/3 (33.3%)		1/16 (6.3%)		2/6 (33.3%)		14/69 (20.3%)		18/84 (21.4%)		7/41 (17.1%)
Dysphonia	1/17 (5.9%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Dyspnoea	2/17 (11.8%)		0/6 (0%)		1/4 (25%)		1/3 (33.3%)		3/16 (18.8%)		2/6 (33.3%)		13/69 (18.8%)		21/84 (25%)		11/41 (26.8%)
Dyspnoea exertional	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Epistaxis	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		1/3 (33.3%)		3/16 (18.8%)		1/6 (16.7%)		11/69 (15.9%)		7/84 (8.3%)		6/41 (14.6%)
Hypoxia	2/17 (11.8%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		8/69 (11.6%)		0/84 (0%)		0/41 (0%)
Lung infiltration	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Nasal congestion	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		7/69 (10.1%)		0/84 (0%)		0/41 (0%)
Oropharyngeal pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		2/6 (33.3%)		12/69 (17.4%)		9/84 (10.7%)		0/41 (0%)
Pleural effusion	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		9/69 (13%)		0/84 (0%)		0/41 (0%)
Pleuritic pain	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pulmonary fibrosis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pulmonary oedema	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Respiratory failure	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Rhinitis allergic	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Rhinorrhoea	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Sinus congestion	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Wheezing	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		7/69 (10.1%)		0/84 (0%)		0/41 (0%)
Hiccups	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		5/69 (7.2%)		0/84 (0%)		0/41 (0%)
Sinus pain	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/17 (5.9%)		1/6 (16.7%)		1/4 (25%)		2/3 (66.7%)		4/16 (25%)		2/6 (33.3%)		16/69 (23.2%)		9/84 (10.7%)		0/41 (0%)
Decubitus ulcer	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Dermatitis acneiform	0/17 (0%)		1/6 (16.7%)		1/4 (25%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Dry skin	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Ecchymosis	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Erythema	0/17 (0%)		2/6 (33.3%)		0/4 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)		0/69 (0%)		7/84 (8.3%)		2/41 (4.9%)
Macule	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Night sweats	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		4/69 (5.8%)		0/84 (0%)		0/41 (0%)
Pain of skin	0/17 (0%)		0/6 (0%)		0/4 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Palmar erythema	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Panniculitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Petechiae	2/17 (11.8%)		2/6 (33.3%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		11/69 (15.9%)		7/84 (8.3%)		4/41 (9.8%)
Plantar erythema	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pruritus	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		4/16 (25%)		1/6 (16.7%)		10/69 (14.5%)		6/84 (7.1%)		1/41 (2.4%)
Pruritus allergic	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Purpura	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Rash	2/17 (11.8%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		1/6 (16.7%)		14/69 (20.3%)		11/84 (13.1%)		1/41 (2.4%)
Rash macular	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Rash maculo-papular	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		3/16 (18.8%)		0/6 (0%)		9/69 (13%)		0/84 (0%)		0/41 (0%)
Rash papular	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Skin disorder	0/17 (0%)		0/6 (0%)		1/4 (25%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Skin lesion	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Skin ulcer	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Urticaria	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Hyperhidrosis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		9/69 (13%)		0/84 (0%)		0/41 (0%)
Vascular disorders
Hypertension	0/17 (0%)		1/6 (16.7%)		0/4 (0%)		1/3 (33.3%)		3/16 (18.8%)		1/6 (16.7%)		12/69 (17.4%)		6/84 (7.1%)		1/41 (2.4%)
Hypotension	1/17 (5.9%)		2/6 (33.3%)		0/4 (0%)		0/3 (0%)		4/16 (25%)		0/6 (0%)		14/69 (20.3%)		12/84 (14.3%)		4/41 (9.8%)
Ischaemia	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Phlebitis	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Thrombophlebitis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Venous thrombosis	1/17 (5.9%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		0/84 (0%)		0/41 (0%)
Pallor	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		1/84 (1.2%)		3/41 (7.3%)
Haematoma	0/17 (0%)		0/6 (0%)		0/4 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)		0/69 (0%)		5/84 (6%)		2/41 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title	Pfizer ClinicalTrials.gov Call Center
Organization	Pfizer, Inc.
Phone	1-800-718-1021
Email	ClinicalTrials.gov_Inquiries@pfizer.com

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01546038

Other Study ID Numbers:

B1371003
2012-000684-24

First Posted:

Mar 7, 2012

Last Update Posted:

Mar 3, 2020

Last Verified:

Feb 1, 2020