A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients
BRIGHT 1012
An Open-label Phase 1b Study of PF-04449913 (Glasdegib) in Combination With Azacitidine in Patients With Previously Untreated Higher-Risk Myelodysplastic Syndrome, Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia
3 other identifiers
interventional
73
6 countries
33
Brief Summary
This multi center open label Phase 1b study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of glasdegib (PF-04449913) when combined with azacitidine in patients with previously untreated Higher Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). This clinical study includes two components: (a) a safety lead in cohort (LIC) and (b) an expansion phase with an AML cohort and an MDS cohort.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2015
Longer than P75 for phase_1
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 13, 2015
CompletedFirst Posted
Study publicly available on registry
February 20, 2015
CompletedStudy Start
First participant enrolled
April 28, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 29, 2020
CompletedResults Posted
Study results publicly available
March 5, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 7, 2022
CompletedJanuary 19, 2024
April 1, 2023
4.8 years
February 13, 2015
January 19, 2021
April 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. Grades of AEs were defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE.
maximum of approximately 15 months
Number of Participants With Serious Adverse Events (SAEs) in the LIC
A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.
maximum of approximately 15 months
Number of Participants With Laboratory Abnormalities in the LIC
Hematology lab parameters included activated partial thromboplastin time, hemoglobin, prothrombin international normalized ratio, lymphocyte, neutrophil, platelet, white blood cell; chemistry parameters included alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, creatine phosphokinase, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate. Grades of lab abnormalities were defined by NCI CTCAE version 4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated. Grade 1-4 results are reported.
maximum of approximately 16 months
Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts
Percentage of participants achieving CR as defined by the 2017 European Leukemia Net (ELN) Response Criteria for all participants with AML and modified International Working Group (IWG) criteria (2006) for all participants with MDS in the expansion cohorts. For AML cohort, CR was defined as neutrophils ≥ 1 x 10\^9/L, platelets ≥ 1 x 10\^11/L, percentage of bone marrow blasts (BMB) \<5% with no peripheral blasts and no blasts with Auer rods, no extramedullary disease (EMD), and transfusion independent. For MDS cohort, CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10\^9/L, platelets ≥1 x 10\^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks.
maximum of 23 months in AML cohort and 34 months in MDS cohort
Secondary Outcomes (18)
Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC
maximum of approximately 16 months
Number of Participants With Efficacy Measures Other Than CR in the LIC
maximum of approximately 16 months
Number of Participants With TEAEs in the AML and MDS Cohorts
maximum of around 23 months in AML cohort and 40 months in MDS cohort
Number of Participants With SAEs in the AML and MDS Cohorts
maximum of around 23 months in AML cohort and 40 months in MDS cohort
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts
maximum of around 23 months in AML cohort and 40 months in MDS cohort
- +13 more secondary outcomes
Study Arms (2)
Arm A
EXPERIMENTALMDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2
Arm B
EXPERIMENTALAML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2
Interventions
Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles
Eligibility Criteria
You may qualify if:
- Patients must have previously untreated MDS, AML, or CMML according to the WHO 2016 classification.
- MDS patients must have Intermediate (\>3 to 4.5 points), High Risk (\>4.5 - 6) or Very High Risk (\>6 points) disease according to the Revised International Prognostic Scoring System 2012 (IPSS-R).
- Clinical indication for treatment with azacitidine for MDS or AML.
You may not qualify if:
- Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
- Patients with known active CNS leukemia.
- Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (33)
University of Alabama at Birmingham the Kirklin Clinic
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Smilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, 06510, United States
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Stony Brook University Hospital Cancer Center
Stony Brook, New York, 11794, United States
Stony Brook University
Stony Brook, New York, 11794, United States
Montefiore Einstein Center for Cancer
The Bronx, New York, 10461, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Duke University Health System: Adult Bone Marrow Transplant Clinic
Durham, North Carolina, 27705, United States
Duke University Health System, Duke University Hospital
Durham, North Carolina, 27710, United States
Duke University Health System
Durham, North Carolina, 27710, United States
Investigational Chemotherapy Service
Durham, North Carolina, 27710, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195, United States
Henry-Joyce Cancer Center
Nashville, Tennessee, 37232, United States
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Huntsman Cancer Hospital
Salt Lake City, Utah, 84112, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Seattle Cancer Care Alliance (SCCA)
Seattle, Washington, 98109, United States
University of Washington Medical Center (UWMC)
Seattle, Washington, 98195, United States
Ziekenhuis Netwerk Antwerpen - Campus Stuivenberg
Antwerp, 2060, Belgium
UZ Leuven
Leuven, 3000, Belgium
Tom Baker Cancer Center
Calgary, Alberta, T2N 4N2, Canada
University Of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
CHU d'Amiens-Picardie - Hopital SUD
Amiens, 80054, France
Hopital Saint-Louis (AP-HP) - Service Hematologie Senior
Paris, 75475, France
Hospices Civils de Lyon - Hopital Lyon Sud- Hematologie
Pierre-Bénite, 69495, France
CHU de Tours-Hopital Bretonneau-Centre Regional de cancerologie Henry Kaplan
Tours, 37044, France
Staedtisches Klinikum Braunschweig gGmbH
Braunschweig, 38114, Germany
King's College Hospital
London, SE5 9RS, United Kingdom
The Newcastle Hospitals NHS Foundation Trust
Newcastle upon Tyne, NE7 7DN, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU, United Kingdom
Related Publications (1)
Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O'Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Ann Hematol. 2022 Aug;101(8):1689-1701. doi: 10.1007/s00277-022-04853-4. Epub 2022 Apr 30.
PMID: 35488900DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 13, 2015
First Posted
February 20, 2015
Study Start
April 28, 2015
Primary Completion
January 29, 2020
Study Completion
March 7, 2022
Last Updated
January 19, 2024
Results First Posted
March 5, 2021
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will not share
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.