Clinical Trials List
Protocol NumberB1371019
NCT Number(ClinicalTrials.gov Identfier)NCT03416179
2018-01-31 - 2026-02-08
Phase III
Recruiting5
ICD-10C92
Myeloid leukemia
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
-
Trial Applicant
Syneos Health
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Sponsor
Pfizer, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Po-Shen Ko Division of Hematology & Oncology
- Yao-Chung Liu Division of Hematology & Oncology
- Hao-Yuan Wang Division of Hematology & Oncology
- Liang-Tsai Hsiao Division of Hematology & Oncology
- Sheng-Hsuan Chien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
101 Recruiting
Audit
None
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- 邱倫瑋 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 高小雯 Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
- Hung Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- MING YAO Division of General Internal Medicine
- Chieh-Lung Cheng Division of General Internal Medicine
- - - Division of General Internal Medicine
- Sheng-chieh Chou Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
- - - Division of General Internal Medicine
- Huai-Hsuan Huang Division of General Internal Medicine
- SHAN-CHI YU Division of General Internal Medicine
- 林建廷 無
- Tai-Chung Huang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Acute Myeloid Leukemia, AML
Objectives
Primary Objective: To demonstrate that glasdegib is superior toplacebo in combination with azacitidine(non-intensive study) or cytarabine anddaunorubicin (intensive study) in prolonging OSin subjects with untreated AML.
Test Drug
Glasdegib (PF-04449913)
Active Ingredient
Glasdegib (PF-04449913)
Dosage Form
tablet
Dosage
25, 100
Endpoints
Primary Outcome Measures :
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.
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.
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.
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.
Inclution Criteria
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:
a. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
b. Have medically confirmed ovarian failure; or
c. 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).
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:
a. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
b. Have medically confirmed ovarian failure; or
c. 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
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).
1
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 (Appendix 5).
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.
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).
1
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 (Appendix 5).
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.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
720 participants
