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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Low dose ARA-C (LDAC); Drug: PF-04449913; Drug: PF-04449913; Drug: PF-04449913; Drug: PF-04449913; Drug: Decitabine; Drug: Daunorubicin; Drug: Cytarabine

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre @ Hamilton Health Sciences
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Centre de Sante et de Services Sociaux (CSSS) Champlain - Charles-Le Moyne
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitatsmedizin Berlin
  • Berlin, Germany, 12203
    • Charite -Universitatsmedizin Berlin - Campus Benjamin Franklin
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein
  • Magdeburg, Germany, 39120
    • Universitaetsklinikum Magdeburg A.oe.R.
  • Mainz, Germany, 55131
    • Johannes Gutenberg-Universitaet Mainz
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
  • Baden-wuerttemberg
    • Ulm, Baden-wuerttemberg, Germany, 89081
      • Universitaetsklinikum Ulm
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Johann Wolfgang Goethe University
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover
• Italy
  • Milano, Italy, 20162
    • Asst Grande Ospedale Metropolitano Niguarda
  • Rome, Italy, 00161
    • Policlinico Universitario "Umberto I" Universita degli Studi "La Sapienza" Sezione di Ematologia
  • Torino, Italy, 10126
    • A.O. Citta della Salute e della Scienza di Torino - S.C. Ematologia
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Integrata di Udine
  • Province OF Bologna
    • Bologna, Province OF Bologna, Italy, 40138
      • Policlinico S. Orsola-Malpighi
• Poland
  • Lodz, Poland, 93-513
    • Oddzial Hematologii Z pododzialem chemioterapii-Klinika Hematologii Wojewodzkie Wielospecjalistyczne
  • Wroclaw, Poland, 53-439
    • Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne Gdanskiego Uniwersytetu Medycznego
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08025
    • Hospital de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249-6909
      • University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92093-0698
      • UC San Diego Moores Cancer Center
    • La Jolla, California, United States, 92037-0845
      • UC San Diego Moores Cancer Center - Investigational Drug Services
    • La Jolla, California, United States, 92037
      • UC San Diego Medical Center - La Jolla
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology Clinic
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center / Investigational Drug Services
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center Drug Information Center
    • Los Angeles, California, United States, 90033
      • LAC & USC Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Drug lnformation/lnvestigational Drugs
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center - Hillcrest
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • H.Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
    • Atlanta, Georgia, United States, 30322
      • Investigational Drug Service, Emory University Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine Developmental Therapeutics Institute
    • Chicago, Illinois, United States, 60637
      • The University of Chicago's Medical Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Clinical Research Center
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center and Medical Pavilion
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute (DFCI)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Ann Arbor, Michigan, United States, 48109-2800
      • University of Michigan Comprehensive Cancer Center Clinical Trials Office
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center - West County
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Siteman Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital North Campus
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Division of Bone Marrow Transplant & Leukemia
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • University of Washington-Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm A (Phase 1B); PF-04449913 in combination with low dose ARA-C (LDAC)	Drug: Low dose ARA-C (LDAC); Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28-days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)
EXPERIMENTAL: Arm B (Phase 1B); PF-04449913 in combination with Decitabine	Drug: PF-04449913; PF-04449913 administered orally and continuously for 28-days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913); 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: PF-04449913; PF-04449913 administered orally and continuously for 28 days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913); 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: PF-04449913; PF-04449913 administered orally and continuously for 28 days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913); 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: Low dose ARA-C (LDAC); Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28-days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days.; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days; Drug: PF-04449913; PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B	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.	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
Percentage of Participants With Complete Response (CR) at Phase 2 Fit	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.	4 years
Overall Survival (OS) at Phase 2 Unfit	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.	Randomization to Follow-up (4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) at Phase 1B	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.	First dose to Follow-up (4 years)
Overall Survival (OS) at Phase 2 Fit	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.	First dose to Follow-up (4 years)
Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B	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).	4 years
Percentage of Participants With Complete Response (CR) at Phase 2 Unfit	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.	4 years
Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit	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).	4 years
Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit	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).	4 years
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	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.	Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
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	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.	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 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	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.	Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
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	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.	Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B 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.	Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B 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.	Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B 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, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
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	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.	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)
Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline	Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.	Baseline (Induction Cycle 1/Day -3 pre-dose)
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3	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.	Induction Cycle 1/Day 3, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10	Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.	Induction Cycle 1/Day 10, 1 Hour Post dose
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B	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.	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)
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In	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.	Induction Cycle 1/Lead-in, 1 Hour Post dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3	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.	Induction Cycle 1/Day 3, 1 Hour Post dose
Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and 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.	Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.	Induction Cycle 1/Day 3, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.	Induction Cycle 1/Day 10, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.	Consolidation Cycle 1/Day 1, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.	Consolidation Cycle 1/Day 10, Pre-dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment	Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.	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)
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit	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.	Baseline (Induction Cycle 1/Day -3 pre-dose)
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3	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.	Induction Cycle 1/Day 3, 1 Hour Post dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10	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.	Induction Cycle 1/Day 10, 1 Hour Post dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment	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.	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 of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1	Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.	Cycle 1/Day 1, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10	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.	Cycle 1/Day 10, Pre-dose
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit	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.	Baseline (Cycle 1/Day 1 pre-dose)
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1	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.	Cycle 1/Day 1, 1 Hour Post-dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment	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.	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)
Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3	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.	Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose
Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment	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.	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)
Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment	Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.	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)
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit	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 (Induction Cycle 1/Day -3 pre-dose)
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit	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.	Baseline (Cycle 1/Day 1 pre-dose)
Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit	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.	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)
Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit	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.	Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B	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.	1 year
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit	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.	1 year
Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)	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.	4 years
Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)	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.	4 years
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B	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.	4 years
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)	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.	4 years
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)	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.	4 years
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit	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.	4 years

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Perez-Simon JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. doi: 10.1007/s00277-021-04465-4. Epub 2021 Mar 19. Erratum In: Ann Hematol. 2021 Jul;100(7):1917-1918.
• Lin S, Shaik N, Chan G, Cortes JE, Ruiz-Garcia A. An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure. Cancer Chemother Pharmacol. 2020 Oct;86(4):451-459. doi: 10.1007/s00280-020-04132-x. Epub 2020 Sep 3.
• Cortes JE, Heidel FH, Fiedler W, Smith BD, Robak T, Montesinos P, Candoni A, Leber B, Sekeres MA, Pollyea DA, Ferdinand R, Ma WW, O'Brien T, O'Connell A, Chan G, Heuser M. Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy. J Hematol Oncol. 2020 Jul 14;13(1):92. doi: 10.1186/s13045-020-00929-8.
• Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. doi: 10.1038/s41375-018-0312-9. Epub 2018 Dec 16.
• Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. doi: 10.1002/ajh.25238. Epub 2018 Sep 9.
• Savona MR, Pollyea DA, Stock W, Oehler VG, Schroeder MA, Lancet J, McCloskey J, Kantarjian HM, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Cortes JE. Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with Standard Chemotherapy in Patients with AML or High-Risk MDS. Clin Cancer Res. 2018 May 15;24(10):2294-2303. doi: 10.1158/1078-0432.CCR-17-2824. Epub 2018 Feb 20.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2012
• Primary Completion (ACTUAL): January 3, 2017
• Study Completion (ACTUAL): March 4, 2019

Study Registration Dates

• First Submitted: March 1, 2012
• First Submitted That Met QC Criteria: March 1, 2012
• First Posted (ESTIMATE): March 7, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Myelodysplastic syndrome; Hedgehog Inhibitor; Intensive chemotherapy; glasdegib; LDAC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Decitabine; Cytarabine; Daunorubicin
• Other Study ID Numbers: B1371003; 2012-000684-24 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.