Clinical trial NCT01546038: A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Hedgehog Inhibitor
Acute Myeloid Leukemia
Myelodysplastic syndrome
Intensive chemotherapy
LDAC
glasdegib
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
timeFrame: 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
measure: Percentage of Participants With Complete Response (CR) at Phase 2 Fit
timeFrame: 4 years
measure: Overall Survival (OS) at Phase 2 Unfit
timeFrame: Randomization to Follow-up (4 years)
Secondary outcomes:
measure: Overall Survival (OS) at Phase 1B
timeFrame: First dose to Follow-up (4 years)
measure: Overall Survival (OS) at Phase 2 Fit
timeFrame: First dose to Follow-up (4 years)
measure: Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
timeFrame: 4 years
measure: Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
timeFrame: 4 years
measure: Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
timeFrame: 4 years
measure: Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
timeFrame: 4 years
measure: 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
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
measure: 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
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
measure: 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
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
measure: Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
timeFrame: 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
measure: Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
timeFrame: 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
measure: AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
timeFrame: 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
measure: Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
timeFrame: 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
measure: Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
timeFrame: 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
measure: AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
timeFrame: 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
measure: 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
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
measure: 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
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
measure: 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
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
measure: 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
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
measure: Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
timeFrame: 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
measure: Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
timeFrame: 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
measure: AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
timeFrame: 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
measure: AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
timeFrame: Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
measure: Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
timeFrame: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
measure: Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
timeFrame: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
measure: AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
timeFrame: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
measure: Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
timeFrame: Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10
measure: Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
timeFrame: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
measure: Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
timeFrame: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
measure: AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
timeFrame: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
measure: Number of Participants With Disease-related Gene Mutations at Phase 1B
timeFrame: 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)
measure: Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
timeFrame: Baseline (Induction Cycle 1/Day -3 pre-dose)
measure: Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
timeFrame: Induction Cycle 1/Day 3, 1 Hour Post dose
measure: Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
timeFrame: Induction Cycle 1/Day 10, 1 Hour Post dose
measure: Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
timeFrame: 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)
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
timeFrame: Induction Cycle 1/Lead-in, 1 Hour Post dose
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
timeFrame: Induction Cycle 1/Day 3, 1 Hour Post dose
measure: Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
timeFrame: Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
timeFrame: Induction Cycle 1/Day 3, 1 Hour Post dose
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
timeFrame: Induction Cycle 1/Day 10, 1 Hour Post dose
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
timeFrame: Consolidation Cycle 1/Day 1, 1 Hour Post dose
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
timeFrame: Consolidation Cycle 1/Day 10, Pre-dose
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
timeFrame: 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)
measure: Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
timeFrame: Baseline (Induction Cycle 1/Day -3 pre-dose)
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
timeFrame: Induction Cycle 1/Day 3, 1 Hour Post dose
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
timeFrame: Induction Cycle 1/Day 10, 1 Hour Post dose
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
timeFrame: 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)
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
timeFrame: Cycle 1/Day 1, 1 Hour Post dose
measure: Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
timeFrame: Cycle 1/Day 10, Pre-dose
measure: Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
timeFrame: Baseline (Cycle 1/Day 1 pre-dose)
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
timeFrame: Cycle 1/Day 1, 1 Hour Post-dose
measure: Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
timeFrame: 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)
measure: Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
timeFrame: Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose
measure: Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
timeFrame: 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)
measure: Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
timeFrame: 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)
measure: Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
timeFrame: Baseline (Induction Cycle 1/Day -3 pre-dose)
measure: Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
timeFrame: Baseline (Cycle 1/Day 1 pre-dose)
measure: Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
timeFrame: 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)
measure: Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
timeFrame: Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose
measure: Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
timeFrame: 1 year
measure: Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
timeFrame: 1 year
measure: Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
timeFrame: 4 years
measure: Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
timeFrame: 4 years
measure: Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
timeFrame: 4 years
measure: Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
timeFrame: 4 years
measure: Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
timeFrame: 4 years
measure: Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
timeFrame: 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center - Investigational Drug Services
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC & USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center / Investigational Drug Services
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center Drug Information Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Drug lnformation/lnvestigational Drugs
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology Clinic
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Tampa
country: United States
facility: H.Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Investigational Drug Service, Emory University Clinic
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: Northwestern Medicine Developmental Therapeutics Institute
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago's Medical Center
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center Clinical Trials Office
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital North Campus
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Division of Bone Marrow Transplant & Leukemia
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Siteman Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Institute
state: Ohio
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington-Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre @ Hamilton Health Sciences
state: Ontario
city: Greenfield Park
country: Canada
facility: Centre de Sante et de Services Sociaux (CSSS) Champlain - Charles-Le Moyne
state: Quebec
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden-wuerttemberg
city: Frankfurt am Main
country: Germany
facility: Johann Wolfgang Goethe University
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Lower Saxony
city: Berlin
country: Germany
facility: Charite -Universitatsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg A.oe.R.
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universitaet Mainz
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
state: Province OF Bologna
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Rome
country: Italy
facility: Policlinico Universitario "Umberto I" Universita degli Studi "La Sapienza" Sezione di Ematologia
city: Torino
country: Italy
facility: A.O. Citta della Salute e della Scienza di Torino - S.C. Ematologia
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Gdanskiego Uniwersytetu Medycznego
state: Pomorskie
city: Lodz
country: Poland
facility: Oddzial Hematologii Z pododzialem chemioterapii-Klinika Hematologii Wojewodzkie Wielospecjalistyczne
city: Wroclaw
country: Poland
facility: Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucia
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.