A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia (BRIGHT AML1019)

April 20, 2023 updated by: Pfizer

A RANDOMIZED (1:1), DOUBLE-BLIND, MULTI-CENTER, PLACEBO CONTROLLED STUDY EVALUATING INTENSIVE CHEMOTHERAPY WITH OR WITHOUT GLASDEGIB (PF-04449913) OR AZACITIDINE (AZA) WITH OR WITHOUT GLASDEGIB IN PATIENTS WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA

Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population).

Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Two separate registration trials conducted under one protocol number are proposed to adequately and independently evaluate the addition of glasdegib in intensive and non-intensive chemotherapy populations. Each study will have an experimental treatment arm and a placebo arm. Endpoints are the same for each study except where specifically indicated.

Assignment to the Intensive Study or the Non-Intensive Study will be made by the Investigator based on the 2017 European LeukemiaNet (ELN) recommendations.

Study B1371019 is a randomized (1:1), double-blind, multi-center, placebo controlled study of chemotherapy in combination with glasdegib versus chemotherapy in combination with placebo in adult patients with previously untreated AML.

Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population).

Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
730

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • St Vincent's Hospital Sydney
      • Kogarah, New South Wales, Australia, 2217
        • St George Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
  • Austria
      • Salzburg, Austria, 5020
        • Landeskrankenhaus Salzburg, Universitatsklinik fur Innere Medizin III der PMU
      • Salzburg, Austria, 5020
        • Uniklinikum Salzburg, Landeskrankenhaus Salzburg
      • Wien, Austria, 1130
        • Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel
  • Belgium
      • Brugge, Belgium, B-8000
        • AZ Sint-Jan Brugge-Oostende AV
      • Brussels, Belgium, B-1090
        • Universitaire Ziekenhuizen Brussel (UZ Brussel)
      • Brussels, Belgium, B-1090
        • Universitaire Ziekenhuizen Brussel
      • Leuven, Belgium, B-3000
        • Universitaire Ziekenhuizen Leuven
  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Health Sciences Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • CIUSSS de L'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Royal University Hospital
  • China
      • Shanghai, China, 200025
        • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Anhui
      • Hefei, Anhui, China, 230001
        • The First Affiliated Hospital of USTC, Anhui Provincial Hospital
      • Hefei, Anhui, China, 230071
        • Anhui Provincial Hospital
    • Fujian
      • Fuzhou, Fujian, China, 350001
        • Fujian Medical University Union Hospital
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Guangdong Provincial People's Hospital
      • Guangzhou, Guangdong, China, 510317
        • Guangdong Second Provincial General Hospital
    • Hebei
      • Langfang, Hebei, China, 065201
        • Hebei Yanda Lu Daopei Hospital
    • Henan
      • Zhengzhou, Henan, China, 450008
        • Henan Cancer Hospital
      • Zhengzhou, Henan, China, 450003
        • Henan Provincial People's Hospital/Hematology Department
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China Hospital, Sichuan University
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • The First Affiliated Hospital College of Medicine, Zhejiang University
  • Czechia
      • Brno, Czechia, 625 00
        • Interni hematologicka a onkologicka klinika, Fakultni nemocnice Brno
      • Brno, Czechia, 625 00
        • Nemocniční lékárna
      • Ostrava - Poruba, Czechia, 708 52
        • Ustavni lekarna
      • Ostrava-Poruba, Czechia, 708 52
        • Klinika Hematoonkologie
      • Praha 10, Czechia, 100 34
        • Interní hematologická klinika, Fakultni nemocnice Královské Vinohrady
      • Praha 10, Czechia, 100 34
        • Ustavni lekarna
  • France
      • Créteil, France, 94010
        • CHU Henri Mondor
      • Nantes cedex, France, 44093
        • CHU de Nantes hotel Dieu
      • Nantes cedex 1, France, 44093
        • CHU de NANTES
      • Paris, France, 75010
        • Hopital Saint Louis
      • Pierre-Benite cedex, France, 69495
        • Centre Hospitalier Lyon Sud - Service d'Hematologie
      • Villejuif cedex, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
    • Bavaria
      • Munich, Bavaria, Germany, 81377
        • Klinikum der Universitaet Muenchen
    • Hesse
      • Marburg, Hesse, Germany, 35032
        • Philipps-Universitaet Marburg
    • North Rhine Westphalia
      • Koeln, North Rhine Westphalia, Germany, 50937
        • Universitatsklinikum Koln
    • North Rhine-westphalia
      • Muenster, North Rhine-westphalia, Germany, 48149
        • Universitaetsklinikum Muenster
  • Hungary
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika, Hematologia Tanszek
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika
      • Győr, Hungary, 9024
        • Petz Aladár Megyei Oktató Kórház, II. Belgyógyászat- Hematológiai Osztály
      • Kaposvar, Hungary, 7400
        • Somogy Megyei Kaposi Mor Oktato Korhaz
      • Nyiregyhaza, Hungary, 4400
        • Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia
      • Nyiregyhaza, Hungary, 4400
        • Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz,
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center (Ein Kerem)
      • Petah Tikva, Israel, 4941492
        • Hemato-oncology ambulatory Service
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center, Beilinson Hospital
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliero Universitaria di Bologna Policlinico S.Orsola Malpighi
      • Siena, Italy, 53100
        • Azienda Ospedaliera Universitaria Senese
    • AN
      • Torette Di Ancona, AN, Italy, 60126
        • SOD Farmacia-Dipt dei servizi -AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi
    • Ancona
      • Torrette Di Ancona, Ancona, Italy, 60126
        • AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi, Clinica Di Ematologia
    • FE
      • Cona, Ferrara, FE, Italy, 44124
        • A.O.U. di Ferrara- Arcispedale Sant'Anna,
    • PU
      • Pesaro, PU, Italy, 61122
        • AO Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro -
    • SI
      • Siena, SI, Italy, 53100
        • Azienda Ospedaliera Universitaria Senese.
  • Japan
      • Akita, Japan, 010-8543
        • Akita University Hospital
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
      • Kumamoto, Japan, 860-0008
        • National Hospital Organization Kumamoto Medical Center
      • Nagasaki, Japan, 852-8501
        • Nagasaki University Hospital
      • Tokyo, Japan, 160-0023
        • Tokyo Medical University Hospital
    • Aichi
      • Nagoya, Aichi, Japan, 466-8650
        • Japanese Red Cross Nagoya Daini Hospital
    • Fukui
      • Yoshida-gun, Fukui, Japan, 910-1193
        • University of Fukui Hospital
    • Gunma
      • Maebashi, Gunma, Japan, 371-8511
        • Gunma University Hospital
    • Hyogo
      • Kobe-shi, Hyogo, Japan, 650-0017
        • Kobe University Hospital
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 232-0024
        • Yokohama City University Medical Center
    • Miyagi
      • Sendai, Miyagi, Japan, 980-8574
        • Tohoku University Hospital
    • Osaka
      • Osaka-City, Osaka, Japan, 545-8586
        • Osaka City University Hospital
      • Osaka-Sayama, Osaka, Japan, 589-8511
        • Kindai University Hospital
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center
    • Tokyo
      • Tachikawa, Tokyo, Japan, 190-0014
        • National Hospital Organization Disaster Medical Center
  • Korea, Republic of
      • Busan, Korea, Republic of, 47392
        • Inje University Busan Paik Hospital
      • Daegu, Korea, Republic of, 42601
        • Keimyung University Dongsan Hospital
      • Incheon, Korea, Republic of, 21565
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 03722
        • Clinical Trial Center, Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea Seoul St. Mary's Hospital
    • Jeollabuk-do
      • Jeonju-si, Jeollabuk-do, Korea, Republic of, 54907
        • Chonbuk National University Hospital
  • Mexico
    • MÉX
      • México, MÉX, Mexico, 14080
        • Instituto Nacional de Cancerologia
    • Nuevo LEON
      • Monterrey, Nuevo LEON, Mexico, 64460
        • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
  • Poland
      • Gdansk, Poland, 80-214
        • Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne
      • Lodz, Poland, 93-513
        • Wwcoit Im. M. Kopernika W Lodzi
  • Romania
      • Bucharest, Romania, 010825
        • Sp. Clinic de Urgenta Militar Central Dr. Carol Davila
      • Bucuresti, Romania, 030171
        • Spitalul Clinic Coltea, Clinica de Hematologie
    • Cluj
      • Cluj-Napoca, Cluj, Romania, 400124
        • Institutul Oncologic 'Prof. Dr. Ion Chiricuta'
    • Dolj
      • Craiova, Dolj, Romania, 200136
        • Spitalul Clinic Municipal Filantropia Craiova, Sectia Clinica Hematologie
  • Russian Federation
      • Moscow, Russian Federation, 129301
        • State Budgetary Healthcare Institution of Moscow
      • Nizhniy Novgorod, Russian Federation, 603126
        • SBHI NNR NN RCH n. a. N.A. Semashko
      • Ryazan, Russian Federation, 390039
        • State Budgetary Institution of Ryazan Region 'Regional Clinical Hospital' (SBI RR RCH)
      • Saint Petersburg, Russian Federation, 197341
        • V.A Almazov NMRC
  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu i Sant Pau
      • Lleida, Spain, 25198
        • Hospital Universitario Arnau de Vilanova
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Hospital Universitari i Politècnic La Fe
  • Sweden
      • Orebro, Sweden, 701 85
        • Universitetssjukhuset Orebro
      • Stockholm, Sweden, 141 86
        • Karolinska Universitetssjukhuset Huddinge
  • Taiwan
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Taipei, Taiwan, 112
        • Koo Foundation Sun Yat-Sen Cancer Center
      • Taoyuan City, Taiwan, 333
        • Chang Gung Memorial Hospital-Linkou Branch
  • United Kingdom
      • London, United Kingdom, W12 0HS
        • Imperial College Healthcare NHS Trust
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
    • WEST Midlands
      • Birmingham, WEST Midlands, United Kingdom, B15 2TH
        • University Hospitals Birmingham NHS Foundation Trust
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Hematology/Oncology Clinic
      • Los Angeles, California, United States, 90095
        • UCLA Ronald Reagan Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine
      • Los Angeles, California, United States, 90095
        • UCLA Drug Information/Investigational Drugs
      • Orange, California, United States, 92868-3201
        • UC Irvine Health - Chao Family Comprehensive Cancer Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
      • San Francisco, California, United States, 94143
        • UCSF Helen Diller Family Comprehensive Cancer Center
      • Westlake Village, California, United States, 91361
        • UCLA Hematology/Oncology - Westlake Village
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center
      • Augusta, Georgia, United States, 30912
        • Georgia Cancer Center at Augusta University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center Investigational Drug Pharmacy
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • MidAmerica Division, Inc., c/o Research Medical Center
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health/Monter Cancer Center
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
      • Portland, Oregon, United States, 97239
        • OHSU Center for Health and Healing
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Centennial Medical Center
      • Nashville, Tennessee, United States, 37203
        • TriStar Bone Marrow Transplant
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center
      • San Antonio, Texas, United States, 78229
        • Blood Cancer and Stem Cell Transplant Clinic
      • San Antonio, Texas, United States, 78229
        • Methodist Healthcare System of San Antonio
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the Intensive and Non Intensive study (unless where indicated):

  1. Subjects with untreated AML according to the World Health Organization (WHO) 2016 Classification2, including those with:

    • AML arising from MDS or another antecedent hematologic disease (AHD).
    • AML after previous cytotoxic therapy or radiation (secondary AML).
  2. 18 years of age (In Japan, 20 years of age).

  3. Adequate Organ Function as defined by the following:

    • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) 3 x upper limit of normal (ULN), excluding subjects with liver function abnormalities due to underlying malignancy.
    • Total serum bilirubin 2 x ULN (except subjects with documented Gilbert's syndrome).
    • Estimated creatinine clearance 30 mL/min as calculated using the standard method for the institution.
  4. QTc interval 470 msec using the Fridericia correction (QTcF).

  5. All anti cancer treatments (unless specified) should be discontinued 2 weeks from study entry, for example: targeted chemotherapy, radiotherapy, investigational agents, hormones, anagrelide or cytokines.

    • For control of rapidly progressing leukemia, all trans retinoic acid (ATRA), hydroxyurea, and/or leukopheresis may be used before and for up to 1 week after the first dose of glasdegib.
  6. Serum or urine pregnancy test (for female subjects of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (hCG) negative at screening.
  7. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use at least one highly effective method of contraception throughout the study and for 180 days after the last dose of azacitidine, cytarabine, or daunorubicin; and the last dose of glasdegib or placebo, whichever occurs later.

  8. Female subjects of non childbearing potential must meet at least 1 of the following criteria:

    1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    2. Have medically confirmed ovarian failure; or
    3. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.

    All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.

  9. Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
  10. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
  11. Subjects who are willing and able to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow [BM] assessments).

Exclusion Criteria:

Subjects with any of the following characteristics/conditions will not be included in the study:

  1. Acute Promyelocytic Leukemia (APL) and APLwith PML RARA, subjects (WHO 2016 classification).

  2. AML with BCR ABL1 or t(9;22)(q34;q11.2) as a sole abnormality.

    • Complex genetics may include t(9;22) cytogenetic translocation.
  3. Subjects with known active CNS leukemia.
  4. Participation in other clinical studies involving other investigational drug(s) (Phases 1 4) within 4 weeks prior study entry and/or during study participation.
  5. Subjects known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a patient who refuses blood product support.
  6. Subjects with another active malignancy on treatment with the exception of basal cell carcinoma, non melanoma skin cancer, cervical carcinoma in situ. Other prior or concurrent malignancies will be considered on a case by case basis.
  7. Any one of the following ongoing or in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, symptomatic arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms.
  8. Subjects with an active, life threatening or clinically significant uncontrolled systemic infection not related to AML.
  9. Subjects with left ventricular ejection fraction (LVEF) <50% are excluded from the Intensive Chemotherapy Study only.
  10. Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the Intensive Chemotherapy Study only.
  11. Known malabsorption syndrome or other condition that may significantly impair absorption of study medication in the investigator's judgment (eg, gastrectomy, lap band, Crohn's disease) and inability or unwillingness to swallow tablets or capsules.
  12. Current use or anticipated requirement for drugs that are known strong CYP3A4/5 inducers.
  13. Concurrent administration of herbal preparations.
  14. Major surgery or radiation within 4 weeks of starting study treatment.

  15. Documented or suspected hypersensitivity to any one of the following:

    • For subjects assigned to intensive chemotherapy, documented or suspected hypersensitivity to cytarabine (not including drug fever or exanthema, including known cerebellar side effects) or daunorubicin.
    • For subjects assigned to non intensive chemotherapy, documented or suspected hypersensitivity to azacitidine or mannitol.
  16. Known active drug or alcohol abuse.
  17. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  18. Pregnant females or breastfeeding female subjects.
  19. Known recent or active suicidal ideation or behavior.
  20. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A (Intensive Study)
Glasdegib + '7+3' Induction(s)
Drug: glasdegib

Daily Glasdegib (100 mg, PO), beginning on Day 1 and is to continue up to 2 years post randomization.

Following consolidation therapy, glasdegib or placebo will be administered daily for up to 2 years after randomization or until they have minimal residual disease (MRD) negative disease, whichever comes first.

Daily Glasdegib (100 mg, PO) or matching placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy.

Other Names:
  • PF-04449913
Drug: daunorubicin + cytarabine

'7+3' (cytarabine 100 mg/m2, IV for 7 days by continuous infusion and daunorubicin 60 mg/m2 for 3 days).

If a second induction is needed, Investigators may choose either a 5 day cytarabine continuous infusion plus daunorubicin for 2 days ('5+2') or a 7 day cytarabine continuous infusion plus daunorubicin for 3 days ('7+3');

Drug: glasdegib

Glasdegib 100 mg PO QD is to be administered by mouth daily beginning on Day 1 of chemotherapy and will continue if subjects demonstrate reasonable evidence of clinical benefit and do not meet the criteria for progression regardless of any delays/modifications in the chemotherapy treatment.

Subjects will continue glasdegib until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever comes first.

Drug: cytarabine
Consolidation with single agent cytarabine 3 g/m2 IV for adults <60 years and 1 g/m2 for adults 60 years over 3 BID on Days 1, 3, and 5, every 28 days for up to 4 cycles or alternative single agent cytarabine consolidation schedules may be used per local prescribing information.
Procedure: HSCT
If required, and done per standard of care post Induction(s).
Placebo Comparator: Arm B (Intensive Study)
Placebo + '7+3' Induction(s)
Drug: daunorubicin + cytarabine

'7+3' (cytarabine 100 mg/m2, IV for 7 days by continuous infusion and daunorubicin 60 mg/m2 for 3 days).

If a second induction is needed, Investigators may choose either a 5 day cytarabine continuous infusion plus daunorubicin for 2 days ('5+2') or a 7 day cytarabine continuous infusion plus daunorubicin for 3 days ('7+3');

Drug: cytarabine
Consolidation with single agent cytarabine 3 g/m2 IV for adults <60 years and 1 g/m2 for adults 60 years over 3 BID on Days 1, 3, and 5, every 28 days for up to 4 cycles or alternative single agent cytarabine consolidation schedules may be used per local prescribing information.
Procedure: HSCT
If required, and done per standard of care post Induction(s).
Drug: Placebo

Matching placebo (PO) given on Day 1 and is to continue up to 2 years post randomization. Following consolidation therapy, placebo will be administered daily for up to 2 years after randomization or until they have MRD negative disease, whichever comes first.

Daily placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy.

Drug: Placebo
Matching placebo (PO) is to be administered by mouth daily beginning on Day 1 of chemotherapy and will continue if subjects demonstrate reasonable evidence of clinical benefit and do not meet the criteria for progression regardless of any delays/modifications in the chemotherapy treatment. Subjects will continue placebo until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever comes first.
Experimental: Arm A (Non-intensive study)
Glasdegib + azacitidine
Drug: glasdegib

Daily Glasdegib (100 mg, PO), beginning on Day 1 and is to continue up to 2 years post randomization.

Following consolidation therapy, glasdegib or placebo will be administered daily for up to 2 years after randomization or until they have minimal residual disease (MRD) negative disease, whichever comes first.

Daily Glasdegib (100 mg, PO) or matching placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy.

Other Names:
  • PF-04449913
Drug: glasdegib

Glasdegib 100 mg PO QD is to be administered by mouth daily beginning on Day 1 of chemotherapy and will continue if subjects demonstrate reasonable evidence of clinical benefit and do not meet the criteria for progression regardless of any delays/modifications in the chemotherapy treatment.

Subjects will continue glasdegib until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever comes first.

Drug: azacitidine
Azacitidine (75 mg/m2, SC or IV) daily for 7 days, in 28 day cycles for as long as they do not meet the criteria for disease progression, unacceptable toxicity, consent withdrawal, or death.
Placebo Comparator: Arm B (Non-intensive study)
Placebo + azacitidine
Drug: Placebo

Matching placebo (PO) given on Day 1 and is to continue up to 2 years post randomization. Following consolidation therapy, placebo will be administered daily for up to 2 years after randomization or until they have MRD negative disease, whichever comes first.

Daily placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy.

Drug: Placebo
Matching placebo (PO) is to be administered by mouth daily beginning on Day 1 of chemotherapy and will continue if subjects demonstrate reasonable evidence of clinical benefit and do not meet the criteria for progression regardless of any delays/modifications in the chemotherapy treatment. Subjects will continue placebo until disease progression, unacceptable toxicity, consent withdrawal, or death, whichever comes first.
Drug: azacitidine
Azacitidine (75 mg/m2, SC or IV) daily for 7 days, in 28 day cycles for as long as they do not meet the criteria for disease progression, unacceptable toxicity, consent withdrawal, or death.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Intensive Study: Overall Survival (OS)
Time Frame: Baseline up to 25 months
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
Baseline up to 25 months
Non-intensive Study: Overall Survival (OS)
Time Frame: Baseline up to 25 months
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
Baseline up to 25 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Questionnaire
Time Frame: Post-baseline up to Week 8
MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). "Fatigue" was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 numeric rating scale (NRS), where 0 = "not present" and 10 = "as bad as you can imagine". Percentage of participants who had improvement in "fatigue" symptoms reported in this outcome measure.
Post-baseline up to Week 8
Non-intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MDASI-AML/MDS Questionnaire at Week 12
Time Frame: Post-baseline up to Week 12
MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). "Fatigue" was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" and 10 = "as bad as you can imagine". Percentage of participants who had improvement in "fatigue" symptoms reported in this outcome measure.
Post-baseline up to Week 12
Intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)
Time Frame: Day 1 up to maximum of 2 years
Complete remission (CR) was defined based on 2017 European LeukemiaNet (ELN) recommendations. CR: Bone marrow blasts <5 percentage (%); absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) greater than equal to (>=) 1.0*10^9/Liter (L); platelet count >=100*10^9/L. CRMRD-neg: CR with negativity for a genetic marker by reverse transcription quantitative polymerase chain reaction (RT-qPCR), or CR with negativity by Multiparameter Flow Cytometry (MFC).
Day 1 up to maximum of 2 years
Non-intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)
Time Frame: Day 1 up to maximum of 3 years
CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
Day 1 up to maximum of 3 years
Intensive Study: Percentage of Participants With Complete Remission Including Negative Minimal Residual Disease (CRMRD-neg)
Time Frame: Day 1 up to maximum of 2 years
CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
Day 1 up to maximum of 2 years
Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Negative Minimal Residual Disease (CRMRD-neg)
Time Frame: Day 1 up to maximum of 3 years
CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
Day 1 up to maximum of 3 years
Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
Time Frame: Day 1 up to maximum of 2 years
CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC less than (<) 1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods.
Day 1 up to maximum of 2 years
Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
Time Frame: Day 1 up to maximum of 3 years
CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC <1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods.
Day 1 up to maximum of 3 years
Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
Time Frame: Day 1 up to maximum of 2 years
MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods.
Day 1 up to maximum of 2 years
Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
Time Frame: Day 1 up to maximum of 3 years
MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods.
Day 1 up to maximum of 3 years
Intensive Study: Percentage of Participants With Partial Remission (PR)
Time Frame: Day 1 up to maximum of 2 years
PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L.
Day 1 up to maximum of 2 years
Non-intensive Study: Percentage of Participants With Partial Remission (PR)
Time Frame: Day 1 up to maximum of 3 years
PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L.
Day 1 up to maximum of 3 years
Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
Time Frame: Day 1 up to maximum of 3 years
CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
Day 1 up to maximum of 3 years
Intensive Study: Duration of Response (DoRi)
Time Frame: From date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause (maximum up to 2 years)
DoRi: only defined for participants who have ever achieved CRi or better (included CR as well) on study as the time from date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause. CRi: not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. Participants last known to be alive who were free from relapse after CRi or better were censored at the date of last disease assessment that verifies their status.
From date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause (maximum up to 2 years)
Non-intensive Study: Duration of Response (DoRi) or (DoRh)
Time Frame: From date of first achieving CRi/CRh or better to the date of relapse/disease progression after CRi/CRh or better or death due to any cause (maximum up to 3 years)
DoRi: only defined for participants who have ever achieved CRi or better (included CR and CRh) on study as the time from date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause. DoRh: participants who had ever achieved CRh or better (included CR) on study as the time from date of first achieving CRh or better to the date of disease progression, or relapse after CRh or better, or death due to any cause. CRi: not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
From date of first achieving CRi/CRh or better to the date of relapse/disease progression after CRi/CRh or better or death due to any cause (maximum up to 3 years)
Non-intensive Study: Time to Response
Time Frame: From the date of randomization to the first documentation of response (CRi/CRh or better) (maximum up to 3 years)
TTRi:Participants who achieved CRi or better, as the time from date of randomization to first documentation of response(CRi or better).TTRh:Participants who achieved CRh or better, as the time from date of randomization to first documentation of response(CRh or better). CRi:not qualifying for CR, neutrophil<0.5*10^9/L or platelets<50*10^9, absence of extramedullary disease,absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
From the date of randomization to the first documentation of response (CRi/CRh or better) (maximum up to 3 years)
Intensive Study: Event-free Survival (EFS)
Time Frame: From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 2 years)
EFS: Time from the date of randomization to the date of treatment failure (TF), relapse from CR, or death from any cause, whichever comes first. TF was defined as failure to achieve CR during the induction cycle (including the re-induction cycle if there is one) and the event date for TF is the day of randomization. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L.
From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 2 years)
Non-intensive Study: Event-free Survival (EFS)
Time Frame: From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 3 years)
EFS: Time from the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first. TF was defined as failure to achieve CR during the induction cycle (including the re-induction cycle if there is one) and the event date for TF is the day of randomization. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L.
From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 3 years)
Intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score
Time Frame: Day 1 up to maximum of 2 years
MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). The 13 core symptoms and 6 core interference items had highest frequency and/or severity in participants with various cancers and treatment types. It was measured at severity of symptoms and related interference at their worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" or "did not interfere" and 10 = "worst" or "interfered completely".
Day 1 up to maximum of 2 years
Non-intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score
Time Frame: Day 1 up to maximum of 3 years
MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). The 13 core symptoms and 6 core interference items had highest frequency and/or severity in participants with various cancers and treatment types. It was measured at severity of symptoms and related interference at their worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" or "did not interfere" and 10 = "worst" or "interfered completely".
Day 1 up to maximum of 3 years
Intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score
Time Frame: Day 1 up to maximum of 2 years
EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), the EuroQoL visual analogue scale (EQ-VAS). EQ-5D: descriptive system measures a participant's health state on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participant is asked to indicate his/her health state by rating each dimension on a 5-level scale (1=no problem, 5=extreme problem). This rating resulted in a 1-digit number expressing the level selected for that dimension. The digits for the 5 dimensions were combined in a 5-digit number describing the respondent's health state. The EQ-5D index scores ranges from 0 to 1, with 0=worst health state and 1=perfect health.
Day 1 up to maximum of 2 years
Non-intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score
Time Frame: Day 1 up to maximum of 3 years
EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ-5D: descriptive system measures a participant's health state on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participant is asked to indicate his/her health state by rating each dimension on a 5-level scale (1=no problem, 5=extreme problem). This rating resulted in a 1-digit number expressing the level selected for that dimension. The digits for the 5 dimensions were combined in a 5-digit number describing the respondent's health state. The EQ-5D index scores ranges from 0 to 1, with 0=worst health state and 1=perfect health.
Day 1 up to maximum of 3 years
Intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)
Time Frame: Day 1 up to maximum of 2 years
EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ VAS records the respondent's self-rated health on a 20-cm vertical, VAS from 0 (worst imaginable health state) to 100 (best imaginable health state).
Day 1 up to maximum of 2 years
Non-intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)
Time Frame: Day 1 up to maximum of 3 years
EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ VAS records the respondent's self-rated health on a 20-cm vertical, VAS from 0 (worst imaginable health state) to 100 (best imaginable health state).
Day 1 up to maximum of 3 years
Intensive Study: Participants Global Impression of Symptoms (PGIS)
Time Frame: Day 1 up to maximum of 2 years
PGIS: is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time. It uses a 4-point Likert scale as follows: In the last 24 hours, symptoms are: 1-"absent (no symptoms)", 2-"mild", 3-" moderate", 4="severe".
Day 1 up to maximum of 2 years
Non-intensive Study: Participants Global Impression of Symptoms (PGIS)
Time Frame: Day 1 up to maximum of 3 years
PGIS: is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time. It uses a 4-point Likert scale as follows: In the last 24 hours, symptoms are: 1-"absent (no symptoms)", 2-"mild", 3-" moderate", 4="severe".
Day 1 up to maximum of 3 years
Intensive Study: Participants Global Impression of Change (PGIC)
Time Frame: Day 1 up to maximum of 2 years
PGIC: a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 7-point Likert scale anchored by (1) 'very much improved' to (7) 'very much worse', with (4) =' no change'. The PGIC is a measure of "participant rating of global improvement and satisfaction with treatment".
Day 1 up to maximum of 2 years
Non-intensive Study: Participants Global Impression of Change (PGIC)
Time Frame: Day 1 up to maximum of 3 years
PGIC: a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 7-point Likert scale anchored by (1) 'very much improved' to (7) 'very much worse', with (4) =' no change'. The PGIC is a measure of "participant rating of global improvement and satisfaction with treatment".
Day 1 up to maximum of 3 years
Intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 2 years
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Day 1 up to maximum of 2 years
Non-intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 3 years
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Day 1 up to maximum of 3 years
Intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 2 years
A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Day 1 up to maximum of 2 years
Non-intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 3 years
A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Day 1 up to maximum of 3 years
Intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 2 years
Hematology laboratory test included: anemia, hemoglobin increased, international normalized ratio (INR) increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 2 years
Non-intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 3 years
Hematology laboratory test included: anemia, hemoglobin increased, INR increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 3 years
Intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 2 years
Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, creatine phosphokinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 2 years
Non-intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 3 years
Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, CPK increased, creatinine increased, GGT increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 3 years
Intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 2 years
Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 2 years
Non-intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame: Day 1 up to maximum of 3 years
Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 3 years
Intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Time Frame: Induction, Day 10+/-1: pre-dose, 1, 4 hour (hr); Consolidation phase, Day 1: pre-dose, 1, 4 hr
Ctrough of Glasdegib was measured in nanogram per milliliter (ng/mL).
Induction, Day 10+/-1: pre-dose, 1, 4 hour (hr); Consolidation phase, Day 1: pre-dose, 1, 4 hr
Non-intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Time Frame: Pre-dose: Cycle 1 Day 15 and Cycle 2 Day 1
Ctrough of Glasdegib was measured in ng/mL.
Pre-dose: Cycle 1 Day 15 and Cycle 2 Day 1
Intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval
Time Frame: Day 1 up to maximum of 2 years
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 2 years
Non-intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval
Time Frame: Day 1 up to maximum of 3 years
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported.
Day 1 up to maximum of 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 20, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 5, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 17, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 31, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B1371019
  • 2017-002822-19 (EudraCT Number)
  • BRIGHT (Alias Study Number)
  • BRIGHT AML1019 (Other Identifier: Alias Study 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Leukemia, Myeloid, Acute

Clinical Trials on glasdegib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings