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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03416179
• Collaborator: (none)
• Enrollment: 730
• Locations: 149
• Arms: 4
• Actual Duration (Months): 44.9
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute	Drug: glasdegib; Drug: daunorubicin + cytarabine; Drug: azacitidine; Drug: Placebo; Drug: Placebo; Drug: glasdegib; Drug: cytarabine; Procedure: HSCT	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 730 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, multi-center, placebo controlled study.Randomized, double-blind, multi-center, placebo controlled study.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind study.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 20, 2018
• Actual Primary Completion Date: Jun 5, 2020
• Actual Study Completion Date: Jan 17, 2022

Arms and Interventions

Arm	Intervention/Treatment
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: 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: 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: 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).
Experimental: Arm A (Non-intensive study) Glasdegib + azacitidine	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.; 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.
Placebo Comparator: Arm B (Non-intensive study) Placebo + azacitidine	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.; 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.

Outcome Measures

Primary Outcome Measures

1. Intensive Study: Overall Survival (OS) [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.

2. Non-intensive Study: Overall Survival (OS) [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.

Secondary Outcome Measures

1. Intensive Study: Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (DASI-AML/MDS) Questionnaire [Baseline up to 5 years]

2. Non-intensive Study: Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (DASI-AML/MDS) Questionnaire [Baseline up to 5 years]

3. Intensive Study: Percentage of Participants With Complete Remission With Negative Minimal Residual Disease (CRMRD-neg) [Baseline up to 5 years]

4. Non-intensive Study: Percentage of Participants With Complete Remission With Negative Minimal Residual Disease (CRMRD-neg) [Baseline up to 5 years]

5. Intensive Study: Percentage of Participants With Complete Remission (CR) Including Complete Remission With Negative Minimal Residual Disease (CRMRD-neg) [Baseline up to 5 years]

6. Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Complete Remission With Negative Minimal Residual Disease (CRMRD-neg) [Baseline up to 5 years]

7. Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi) [Baseline up to 5 years]

8. Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi) [Baseline up to 5 years]

9. Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS) [Baseline up to 5 years]

10. Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS) [Baseline up to 5 years]

11. Intensive Study: Percentage of Participants With Partial Remission (PR) [Baseline up to 5 years]

12. Non-intensive Study: Percentage of Participants With Partial Remission (PR) [Baseline up to 5 years]

13. Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) [Baseline up to 5 years]

14. Intensive Study: Duration of Response [Baseline up to 5 years]

15. Non-intensive Study: Duration of Response [Baseline up to 5 years]

16. Non-intensive Study: Time to Response [Baseline up to 5 years]

17. Intensive Study: Event-free Survival [Baseline up to 5 years]

18. Non-intensive Study: Event-free Survival [Baseline up to 5 years]

19. Intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score [Baseline up to 5 years]

20. Non-intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score [Baseline up to 5 years]

21. Intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score [Baseline up to 5 years]

22. Non-intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score [Baseline up to 5 years]

23. Intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS) [Baseline up to 5 years]

24. Non-intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS) [Baseline up to 5 years]

25. Intensive Study: Participants Global Impression of Symptoms (PGIS) [Baseline up to 5 years]

26. Non-intensive Study: Participants Global Impression of Symptoms (PGIS) [Baseline up to 5 years]

27. Intensive Study: Participants Global Impression of Change (PGIC) [Baseline up to 5 years]

28. Non-intensive Study: Participants Global Impression of Change (PGIC) [Baseline up to 5 years]

29. Intensive Study: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03 [Baseline up to 5 years]

30. Non-intensive Study: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03 [Baseline up to 5 years]

31. Intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03 [Baseline up to 5 years]

32. Non-intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03 [Baseline up to 5 years]

33. Intensive Study: Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [Baseline up to 5 years]

34. Non-intensive Study: Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE v.4.03 [Baseline up to 5 years]

35. Intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib [1 and 4 hour post dose on Day 1 in first induction therapy; pre-dose, 1, and 4 hours post dose on day 1 in consolidation phase cycles 1 and 2]

36. Non-intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib [Pre-dose, 1 and 4 hour post dose on Day 1 and 15 of cycle 1; pre-dose, 1 and 4 hour post dose on day 1 of cycle 2 and 3]

37. Intensive Study: QTc Interval [Baseline up to 5 years]

38. Non-intensive Study: QTc Interval [Baseline up to 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

1. 18 years of age (In Japan, 20 years of age).

2. 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.

1. QTc interval 470 msec using the Fridericia correction (QTcF).

2. 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.

1. 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.

2. 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.

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

4. Have undergone a documented hysterectomy and/or bilateral oophorectomy;

5. Have medically confirmed ovarian failure; or

6. 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.

1. Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.

2. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.

3. 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.

1. Subjects with known active CNS leukemia.

2. Participation in other clinical studies involving other investigational drug(s) (Phases 1 4) within 4 weeks prior study entry and/or during study participation.

3. Subjects known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a patient who refuses blood product support.

4. 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.

5. 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.

6. Subjects with an active, life threatening or clinically significant uncontrolled systemic infection not related to AML.

7. Subjects with left ventricular ejection fraction (LVEF) <50% are excluded from the Intensive Chemotherapy Study only.

8. Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the Intensive Chemotherapy Study only.

9. 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.

10. Current use or anticipated requirement for drugs that are known strong CYP3A4/5 inducers.

11. Concurrent administration of herbal preparations.

12. Major surgery or radiation within 4 weeks of starting study treatment.

13. 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.

1. Known active drug or alcohol abuse.

2. 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.

3. Pregnant females or breastfeeding female subjects.

4. Known recent or active suicidal ideation or behavior.

5. 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Apr 12, 2019
• Statistical Analysis Plan - Apr 14, 2020

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03416179
• Other Study ID Numbers: B1371019; 2017-002822-19; BRIGHT; BRIGHT AML1019
• First Posted: Jan 31, 2018
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pfizer: glasdegib;; untreated;; Hedgehog Inhibitor
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Azacitidine; Daunorubicin

Study Results

Participant Flow

Recruitment Details

This study evaluated glasdegib in intensive and non-intensive chemotherapy populations. Intensive study: Glasdegib was studied in combination with cytarabine and daunorubicin for the treatment of adult participants with previously untreated acute myeloid leukemia (AML). Non-intensive study: Glasdegib was studied in combination with azacitidine for the treatment of adult participants with previously untreated AML who were not candidates for intensive induction chemotherapy.

Pre-assignment Detail

Results are reported at primary completion date and data has been reported only for primary outcome measures. Data for secondary outcome measures would be posted at secondary completion date. Inadvertently 1 participant was enrolled twice into the study resulting in enrollment number as 730. However, a total of 729 participants were randomized and received treatment in the study.

Arm/Group Title	Intensive Study: Glasdegib + Cytarabine + Daunorubicin	Intensive Study: Placebo + Cytarabine + Daunorubicin	Non-intensive Study: Glasdegib + Azacitidine	Non-intensive Study: Placebo + Azacitidine
Arm/Group Description	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 milligram per square meter (mg/m^2) daily by intravenous (IV) infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with less than (<) 5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram per square meter (gm/m^2) IV for adults greater than or equals to (>=) 60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received hematopoietic stem cell transplantation (HSCT) per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 milligram (mg) tablet orally (PO) once daily (QD) from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive complete remission (CR) minimal residual disease (MRD)-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.	Participants received chemotherapy with azacitidine 75 mg/m^2 subcutaneous (SC) injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.	Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.
Period Title: Overall Study
STARTED	201	203	163	162
COMPLETED	0	0	0	0
NOT COMPLETED	201	203	163	162

Baseline Characteristics

Arm/Group Title	Intensive Study: Glasdegib + Cytarabine + Daunorubicin	Intensive Study: Placebo + Cytarabine + Daunorubicin	Non-intensive Study: Glasdegib + Azacitidine	Non-intensive Study: Placebo + Azacitidine	Total
Arm/Group Description	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 milligram per square meter (mg/m^2) daily by intravenous (IV) infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with less than (<) 5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram per square meter (gm/m^2) IV for adults greater than or equals to (>=) 60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received hematopoietic stem cell transplantation (HSCT) per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 milligram (mg) tablet orally (PO) once daily (QD) from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive complete remission (CR) minimal residual disease (MRD)-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.	Participants received chemotherapy with azacitidine 75 mg/m^2 subcutaneous (SC) injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.	Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.	Total of all reporting groups
Overall Participants	201	203	163	162	729
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.55 (12.60)	55.38 (13.61)	73.19 (7.17)	73.14 (6.82)	63.63 (13.79)
Sex: Female, Male (Count of Participants)
Female	71 35.3%	97 47.8%	97 59.5%	89 54.9%	354 48.6%
Male	130 64.7%	106 52.2%	66 40.5%	73 45.1%	375 51.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 9.5%	12 5.9%	12 7.4%	16 9.9%	59 8.1%
Not Hispanic or Latino	166 82.6%	171 84.2%	140 85.9%	139 85.8%	616 84.5%
Unknown or Not Reported	16 8%	20 9.9%	11 6.7%	7 4.3%	54 7.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	0 0%	0 0%	0 0%	1 0.1%
Asian	66 32.8%	57 28.1%	51 31.3%	44 27.2%	218 29.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 1.5%	3 1.5%	1 0.6%	7 4.3%	14 1.9%
White	110 54.7%	123 60.6%	97 59.5%	99 61.1%	429 58.8%
More than one race	1 0.5%	0 0%	0 0%	0 0%	1 0.1%
Unknown or Not Reported	20 10%	20 9.9%	14 8.6%	12 7.4%	66 9.1%

Outcome Measures

1. Primary Outcome

Title	Intensive Study: Overall Survival (OS)
Description	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.
Time Frame	Baseline up to 25 months

Outcome Measure Data

Analysis Population Description

FA set included all randomized participants.

Arm/Group Title	Intensive Study: Glasdegib + Cytarabine + Daunorubicin	Intensive Study: Placebo + Cytarabine + Daunorubicin
Arm/Group Description	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 milligram per square meter (mg/m^2) daily by intravenous (IV) infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with less than (<) 5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram per square meter (gm/m^2) IV for adults greater than or equals to (>=) 60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received hematopoietic stem cell transplantation (HSCT) per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 milligram (mg) tablet orally (PO) once daily (QD) from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive complete remission (CR) minimal residual disease (MRD)-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.
Measure Participants	201	203
Median (95% Confidence Interval) [months]	17.3	20.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Study: Glasdegib + Cytarabine + Daunorubicin, Intensive Study: Placebo + Cytarabine + Daunorubicin
	Comments	Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio less than (<) 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO + Cytarabine 100 mg/m^2 IV + Daunorubicin 60 mg/m^2 compared to Placebo + Cytarabine 100 mg/m^2 IV + Daunorubicin 60 mg/m^2.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6579
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.755 to 1.532
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Non-intensive Study: Overall Survival (OS)
Description	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.
Time Frame	Baseline up to 25 months

Outcome Measure Data

Analysis Population Description

FA set included all randomized participants.

Arm/Group Title	Non-intensive Study: Glasdegib + Azacitidine	Non-intensive Study: Placebo + Azacitidine
Arm/Group Description	Participants received chemotherapy with azacitidine 75 mg/m^2 subcutaneous (SC) injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.	Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.
Measure Participants	163	162
Median (95% Confidence Interval) [months]	10.3	10.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Study: Glasdegib + Cytarabine + Daunorubicin, Intensive Study: Placebo + Cytarabine + Daunorubicin
	Comments	Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio < 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO QD + Azacitidine compared to Placebo + Azacitidine
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5955
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.775 to 1.388
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Intensive Study: Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (DASI-AML/MDS) Questionnaire
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Non-intensive Study: Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (DASI-AML/MDS) Questionnaire
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Intensive Study: Percentage of Participants With Complete Remission With Negative Minimal Residual Disease (CRMRD-neg)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Non-intensive Study: Percentage of Participants With Complete Remission With Negative Minimal Residual Disease (CRMRD-neg)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Intensive Study: Percentage of Participants With Complete Remission (CR) Including Complete Remission With Negative Minimal Residual Disease (CRMRD-neg)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Complete Remission With Negative Minimal Residual Disease (CRMRD-neg)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Intensive Study: Percentage of Participants With Partial Remission (PR)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Non-intensive Study: Percentage of Participants With Partial Remission (PR)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	Intensive Study: Duration of Response
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	Non-intensive Study: Duration of Response
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	Non-intensive Study: Time to Response
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	Intensive Study: Event-free Survival
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Secondary Outcome

Title	Non-intensive Study: Event-free Survival
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Secondary Outcome

Title	Intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Non-intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Secondary Outcome

Title	Intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

24. Secondary Outcome

Title	Non-intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Secondary Outcome

Title	Intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Secondary Outcome

Title	Non-intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

27. Secondary Outcome

Title	Intensive Study: Participants Global Impression of Symptoms (PGIS)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

28. Secondary Outcome

Title	Non-intensive Study: Participants Global Impression of Symptoms (PGIS)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

29. Secondary Outcome

Title	Intensive Study: Participants Global Impression of Change (PGIC)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

30. Secondary Outcome

Title	Non-intensive Study: Participants Global Impression of Change (PGIC)
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

31. Secondary Outcome

Title	Intensive Study: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

32. Secondary Outcome

Title	Non-intensive Study: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

33. Secondary Outcome

Title	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	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

34. Secondary Outcome

Title	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	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

35. Secondary Outcome

Title	Intensive Study: Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

36. Secondary Outcome

Title	Non-intensive Study: Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

37. Secondary Outcome

Title	Intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Time Frame	1 and 4 hour post dose on Day 1 in first induction therapy; pre-dose, 1, and 4 hours post dose on day 1 in consolidation phase cycles 1 and 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

38. Secondary Outcome

Title	Non-intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Time Frame	Pre-dose, 1 and 4 hour post dose on Day 1 and 15 of cycle 1; pre-dose, 1 and 4 hour post dose on day 1 of cycle 2 and 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

39. Secondary Outcome

Title	Intensive Study: QTc Interval
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

40. Secondary Outcome

Title	Non-intensive Study: QTc Interval
Time Frame	Baseline up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Baseline up to 28 days from last dose of study drug (up to 25 months)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis (SA) set included all subjects who received at least one dose of study drug.
Arm/Group Title	Intensive Study: Glasdegib + Cytarabine + Daunorubicin		Intensive Study: Placebo + Cytarabine + Daunorubicin		Non-intensive Study: Glasdegib + Azacitidine		Non-intensive Study: Placebo + Azacitidine
Arm/Group Description	Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 milligram per square meter (mg/m^2) daily by intravenous (IV) infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with less than (<) 5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram per square meter (gm/m^2) IV for adults greater than or equals to (>=) 60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received hematopoietic stem cell transplantation (HSCT) per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 milligram (mg) tablet orally (PO) once daily (QD) from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive complete remission (CR) minimal residual disease (MRD)-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.		Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction and up to 2 years post randomization or until 2 consecutive CR MRD-negative central laboratory results, whichever came first. Participants were to be followed up for first 2 years from last dose and were to had long term survival follow-up for up to 5 years from randomization of last participant or until death/consent withdrawal.		Participants received chemotherapy with azacitidine 75 mg/m^2 subcutaneous (SC) injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.		Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo up to 2 years following randomization unless 2 consecutive negative MRD assessments. Participants were to be followed up for first 2 years from last dose of drug and were to had long term follow-up for survival for up to 5 years from randomization of last participant in study, or until death, or consent withdrawal.
All Cause Mortality
	Intensive Study: Glasdegib + Cytarabine + Daunorubicin		Intensive Study: Placebo + Cytarabine + Daunorubicin		Non-intensive Study: Glasdegib + Azacitidine		Non-intensive Study: Placebo + Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/198 (33.8%)		60/201 (29.9%)		96/162 (59.3%)		88/160 (55%)
Serious Adverse Events
	Intensive Study: Glasdegib + Cytarabine + Daunorubicin		Intensive Study: Placebo + Cytarabine + Daunorubicin		Non-intensive Study: Glasdegib + Azacitidine		Non-intensive Study: Placebo + Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/198 (42.9%)		91/201 (45.3%)		110/162 (67.9%)		118/160 (73.8%)
Blood and lymphatic system disorders
Anaemia	2/198 (1%)		1/201 (0.5%)		5/162 (3.1%)		2/160 (1.3%)
Febrile neutropenia	18/198 (9.1%)		17/201 (8.5%)		24/162 (14.8%)		18/160 (11.3%)
Neutropenia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Thrombocytopenia	1/198 (0.5%)		3/201 (1.5%)		2/162 (1.2%)		1/160 (0.6%)
Leukocytosis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Splenic necrosis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Cardiac disorders
Atrial fibrillation	3/198 (1.5%)		1/201 (0.5%)		1/162 (0.6%)		1/160 (0.6%)
Cardiac arrest	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Cardiac failure	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		2/160 (1.3%)
Cardiac failure acute	1/198 (0.5%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Myocarditis	1/198 (0.5%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Acute myocardial infarction	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Cardiac failure congestive	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Cardiomyopathy	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Intracardiac mass	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Left ventricular dysfunction	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Myocardial infarction	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Myocardial ischaemia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Atrial flutter	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Bradycardia	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Cardiorenal syndrome	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Ventricular fibrillation	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Eye disorders
Vision blurred	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Gastrointestinal disorders
Colitis	0/198 (0%)		1/201 (0.5%)		4/162 (2.5%)		1/160 (0.6%)
Constipation	1/198 (0.5%)		0/201 (0%)		2/162 (1.2%)		0/160 (0%)
Diarrhoea	1/198 (0.5%)		0/201 (0%)		3/162 (1.9%)		2/160 (1.3%)
Diverticulum intestinal haemorrhagic	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Gastrointestinal haemorrhage	3/198 (1.5%)		0/201 (0%)		2/162 (1.2%)		1/160 (0.6%)
Haematemesis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Intestinal haemorrhage	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Large intestine perforation	0/198 (0%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Lower gastrointestinal haemorrhage	1/198 (0.5%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Neutropenic colitis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Rectal haemorrhage	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Upper gastrointestinal haemorrhage	2/198 (1%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Anal fistula	1/198 (0.5%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Enteritis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Enterocolitis	1/198 (0.5%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Gastric ulcer	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Intussusception	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Proctalgia	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Small intestinal haemorrhage	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Abdominal pain	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		0/160 (0%)
Abdominal distension	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Anal fissure	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Intra-abdominal haematoma	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Mechanical ileus	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Nausea	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Pancreatitis	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		0/160 (0%)
Stomatitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Vomiting	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		2/160 (1.3%)
Gastritis	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Gastrointestinal perforation	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Glossitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Haemorrhoidal haemorrhage	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Haemorrhoids thrombosed	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Ileus	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		0/160 (0%)
Inguinal hernia	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
General disorders
Disease progression	2/198 (1%)		4/201 (2%)		14/162 (8.6%)		22/160 (13.8%)
Multiple organ dysfunction syndrome	0/198 (0%)		1/201 (0.5%)		2/162 (1.2%)		0/160 (0%)
Pyrexia	4/198 (2%)		6/201 (3%)		9/162 (5.6%)		11/160 (6.9%)
Chills	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Malaise	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Mucosal inflammation	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Non-cardiac chest pain	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Asthenia	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Death	0/198 (0%)		0/201 (0%)		4/162 (2.5%)		2/160 (1.3%)
Sudden death	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		1/160 (0.6%)
Fatigue	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		1/160 (0.6%)
General physical health deterioration	0/198 (0%)		0/201 (0%)		0/162 (0%)		3/160 (1.9%)
Soft tissue inflammation	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Hepatobiliary disorders
Cholecystitis acute	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Hyperbilirubinaemia	2/198 (1%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Cholecystitis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Cholelithiasis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Drug-induced liver injury	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Hepatitis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Bile duct stone	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Cholangitis acute	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Immune system disorders
Graft versus host disease	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Graft versus host disease in gastrointestinal tract	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Graft versus host disease in skin	1/198 (0.5%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Hypersensitivity	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Cytokine release syndrome	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Infections and infestations
Arthritis infective	1/198 (0.5%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Bacteraemia	4/198 (2%)		2/201 (1%)		3/162 (1.9%)		4/160 (2.5%)
Bronchopulmonary aspergillosis	1/198 (0.5%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Cellulitis	1/198 (0.5%)		0/201 (0%)		2/162 (1.2%)		7/160 (4.4%)
Clostridium difficile colitis	1/198 (0.5%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Enterobacter bacteraemia	0/198 (0%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Escherichia bacteraemia	1/198 (0.5%)		1/201 (0.5%)		1/162 (0.6%)		1/160 (0.6%)
Infection	3/198 (1.5%)		0/201 (0%)		1/162 (0.6%)		5/160 (3.1%)
Neutropenic sepsis	1/198 (0.5%)		2/201 (1%)		3/162 (1.9%)		5/160 (3.1%)
Perirectal abscess	0/198 (0%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Pneumonia	15/198 (7.6%)		11/201 (5.5%)		26/162 (16%)		35/160 (21.9%)
Pneumonia fungal	2/198 (1%)		2/201 (1%)		2/162 (1.2%)		0/160 (0%)
Pseudomembranous colitis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Sepsis	15/198 (7.6%)		13/201 (6.5%)		13/162 (8%)		9/160 (5.6%)
Septic shock	2/198 (1%)		4/201 (2%)		4/162 (2.5%)		5/160 (3.1%)
Soft tissue infection	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		3/160 (1.9%)
Upper respiratory tract infection	1/198 (0.5%)		0/201 (0%)		2/162 (1.2%)		0/160 (0%)
Urinary tract infection	0/198 (0%)		1/201 (0.5%)		9/162 (5.6%)		4/160 (2.5%)
Anorectal infection	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Atypical pneumonia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Bacterial sepsis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Brain abscess	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Candida pneumonia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Clostridial sepsis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Clostridium bacteraemia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Clostridium colitis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Device related bacteraemia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Diarrhoea infectious	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Disseminated varicella zoster virus infection	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Enterococcal bacteraemia	2/198 (1%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Escherichia sepsis	1/198 (0.5%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Febrile infection	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Fungal infection	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Fungal sepsis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Groin abscess	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Herpes ophthalmic	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Herpes zoster	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Peritonitis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Pseudomonal bacteraemia	3/198 (1.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Pseudomonal sepsis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Pulmonary tuberculosis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Streptococcal sepsis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Urethritis	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Abscess	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Anal abscess	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Bronchitis	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		1/160 (0.6%)
COVID-19	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
COVID-19 pneumonia	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Candida sepsis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Catheter site infection	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Device related infection	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Diverticulitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Herpes dermatitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Infected skin ulcer	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Influenza	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Klebsiella bacteraemia	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Liver abscess	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Lower respiratory tract infection	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Lower respiratory tract infection bacterial	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Otitis media acute	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Periodontitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Pharyngitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Pneumonia staphylococcal	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Post procedural infection	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Pyelonephritis acute	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		2/160 (1.3%)
Rectal abscess	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Skin infection	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Staphylococcal sepsis	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Subdiaphragmatic abscess	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Suspected COVID-19	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Systemic infection	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Systemic mycosis	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Wound infection	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Oral infection	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Injury, poisoning and procedural complications
Fall	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Spinal fracture	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Splenic rupture	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Femoral neck fracture	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Hip fracture	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Lumbar vertebral fracture	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Post procedural complication	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Subdural haematoma	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Subdural haemorrhage	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Tooth fracture	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Transfusion reaction	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Investigations
Blood creatinine increased	0/198 (0%)		1/201 (0.5%)		1/162 (0.6%)		2/160 (1.3%)
Electrocardiogram QT prolonged	13/198 (6.6%)		8/201 (4%)		5/162 (3.1%)		3/160 (1.9%)
Platelet count decreased	1/198 (0.5%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Alanine aminotransferase increased	1/198 (0.5%)		2/201 (1%)		0/162 (0%)		0/160 (0%)
Aspartate aminotransferase increased	1/198 (0.5%)		2/201 (1%)		0/162 (0%)		0/160 (0%)
Blood alkaline phosphatase increased	1/198 (0.5%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Blood bilirubin increased	2/198 (1%)		3/201 (1.5%)		0/162 (0%)		0/160 (0%)
Blood lactate dehydrogenase increased	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Gamma-glutamyltransferase increased	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Neutrophil count decreased	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
C-reactive protein increased	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Creatinine renal clearance decreased	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Electroencephalogram abnormal	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
SARS-CoV-2 test positive	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Weight decreased	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/198 (0%)		1/201 (0.5%)		3/162 (1.9%)		1/160 (0.6%)
Hyperglycaemia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Hypokalaemia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Failure to thrive	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Hyperkalaemia	0/198 (0%)		0/201 (0%)		0/162 (0%)		3/160 (1.9%)
Hyperuricaemia	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		0/160 (0%)
Hyponatraemia	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		1/160 (0.6%)
Hypophosphataemia	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		1/160 (0.6%)
Musculoskeletal and connective tissue disorders
Myalgia	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Back pain	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Osteoarthritis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Soft tissue necrosis	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Synovitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Differentiation syndrome	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Gastrointestinal neoplasm	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Neoplasm progression	0/198 (0%)		0/201 (0%)		0/162 (0%)		2/160 (1.3%)
Neoplasm prostate	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Nervous system disorders
Epilepsy	0/198 (0%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Haemorrhage intracranial	2/198 (1%)		2/201 (1%)		1/162 (0.6%)		1/160 (0.6%)
Syncope	1/198 (0.5%)		0/201 (0%)		1/162 (0.6%)		1/160 (0.6%)
Carotid artery stenosis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Cerebral haemorrhage	1/198 (0.5%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Seizure	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Central nervous system lesion	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Cerebral infarction	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		2/160 (1.3%)
Cerebrovascular accident	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		1/160 (0.6%)
Encephalopathy	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Intracranial aneurysm	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Metabolic encephalopathy	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Partial seizures	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Somnolence	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Psychiatric disorders
Confusional state	0/198 (0%)		1/201 (0.5%)		1/162 (0.6%)		0/160 (0%)
Adjustment disorder with depressed mood	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Hallucination	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Renal and urinary disorders
Acute kidney injury	2/198 (1%)		3/201 (1.5%)		1/162 (0.6%)		1/160 (0.6%)
Chronic kidney disease	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Haematuria	0/198 (0%)		0/201 (0%)		2/162 (1.2%)		1/160 (0.6%)
Renal failure	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Urinary retention	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/198 (0%)		1/201 (0.5%)		3/162 (1.9%)		1/160 (0.6%)
Epistaxis	2/198 (1%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Respiratory failure	1/198 (0.5%)		4/201 (2%)		1/162 (0.6%)		1/160 (0.6%)
Acute respiratory distress syndrome	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Acute respiratory failure	1/198 (0.5%)		3/201 (1.5%)		0/162 (0%)		0/160 (0%)
Hypoxia	1/198 (0.5%)		2/201 (1%)		0/162 (0%)		0/160 (0%)
Lung infiltration	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Pulmonary alveolar haemorrhage	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Pulmonary haemorrhage	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Oropharyngeal pain	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Pneumonia aspiration	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Pneumonitis	0/198 (0%)		0/201 (0%)		0/162 (0%)		3/160 (1.9%)
Pneumothorax	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Pulmonary oedema	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Skin and subcutaneous tissue disorders
Erythema	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Rash	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Rash maculo-papular	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Dermatitis exfoliative generalised	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Drug eruption	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Vascular disorders
Deep vein thrombosis	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		1/160 (0.6%)
Hypotension	1/198 (0.5%)		1/201 (0.5%)		1/162 (0.6%)		1/160 (0.6%)
Embolism	0/198 (0%)		1/201 (0.5%)		0/162 (0%)		0/160 (0%)
Orthostatic hypotension	1/198 (0.5%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Aneurysm ruptured	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Axillary vein thrombosis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Circulatory collapse	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Hypovolaemic shock	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Peripheral ischaemia	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Thrombophlebitis superficial	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Thrombosis	0/198 (0%)		0/201 (0%)		0/162 (0%)		1/160 (0.6%)
Venous thrombosis	0/198 (0%)		0/201 (0%)		1/162 (0.6%)		0/160 (0%)
Other (Not Including Serious) Adverse Events
	Intensive Study: Glasdegib + Cytarabine + Daunorubicin		Intensive Study: Placebo + Cytarabine + Daunorubicin		Non-intensive Study: Glasdegib + Azacitidine		Non-intensive Study: Placebo + Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	194/198 (98%)		195/201 (97%)		153/162 (94.4%)		149/160 (93.1%)
Blood and lymphatic system disorders
Anaemia	101/198 (51%)		97/201 (48.3%)		73/162 (45.1%)		70/160 (43.8%)
Febrile neutropenia	97/198 (49%)		96/201 (47.8%)		22/162 (13.6%)		20/160 (12.5%)
Leukopenia	10/198 (5.1%)		13/201 (6.5%)		11/162 (6.8%)		4/160 (2.5%)
Neutropenia	41/198 (20.7%)		43/201 (21.4%)		35/162 (21.6%)		30/160 (18.8%)
Thrombocytopenia	52/198 (26.3%)		52/201 (25.9%)		37/162 (22.8%)		32/160 (20%)
Cardiac disorders
Sinus tachycardia	11/198 (5.6%)		7/201 (3.5%)		0/162 (0%)		0/160 (0%)
Gastrointestinal disorders
Abdominal pain	31/198 (15.7%)		29/201 (14.4%)		12/162 (7.4%)		10/160 (6.3%)
Constipation	71/198 (35.9%)		61/201 (30.3%)		58/162 (35.8%)		50/160 (31.3%)
Diarrhoea	96/198 (48.5%)		88/201 (43.8%)		36/162 (22.2%)		31/160 (19.4%)
Haemorrhoids	13/198 (6.6%)		19/201 (9.5%)		8/162 (4.9%)		10/160 (6.3%)
Nausea	110/198 (55.6%)		106/201 (52.7%)		55/162 (34%)		44/160 (27.5%)
Vomiting	57/198 (28.8%)		40/201 (19.9%)		35/162 (21.6%)		32/160 (20%)
Abdominal pain upper	12/198 (6.1%)		9/201 (4.5%)		0/162 (0%)		0/160 (0%)
Dyspepsia	12/198 (6.1%)		5/201 (2.5%)		0/162 (0%)		0/160 (0%)
Proctalgia	14/198 (7.1%)		6/201 (3%)		0/162 (0%)		0/160 (0%)
Stomatitis	29/198 (14.6%)		41/201 (20.4%)		0/162 (0%)		0/160 (0%)
General disorders
Asthenia	15/198 (7.6%)		11/201 (5.5%)		15/162 (9.3%)		18/160 (11.3%)
Fatigue	31/198 (15.7%)		32/201 (15.9%)		13/162 (8%)		23/160 (14.4%)
Oedema peripheral	25/198 (12.6%)		32/201 (15.9%)		11/162 (6.8%)		18/160 (11.3%)
Pyrexia	84/198 (42.4%)		84/201 (41.8%)		41/162 (25.3%)		39/160 (24.4%)
Chills	20/198 (10.1%)		11/201 (5.5%)		0/162 (0%)		0/160 (0%)
Mucosal inflammation	12/198 (6.1%)		7/201 (3.5%)		0/162 (0%)		0/160 (0%)
Non-cardiac chest pain	13/198 (6.6%)		8/201 (4%)		0/162 (0%)		0/160 (0%)
Oedema	9/198 (4.5%)		19/201 (9.5%)		0/162 (0%)		0/160 (0%)
Injection site reaction	0/198 (0%)		0/201 (0%)		11/162 (6.8%)		7/160 (4.4%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/198 (0%)		0/201 (0%)		11/162 (6.8%)		0/160 (0%)
Infections and infestations
Pneumonia	32/198 (16.2%)		33/201 (16.4%)		19/162 (11.7%)		15/160 (9.4%)
Upper respiratory tract infection	9/198 (4.5%)		11/201 (5.5%)		12/162 (7.4%)		11/160 (6.9%)
Urinary tract infection	5/198 (2.5%)		11/201 (5.5%)		16/162 (9.9%)		9/160 (5.6%)
Bacteraemia	16/198 (8.1%)		11/201 (5.5%)		0/162 (0%)		0/160 (0%)
Injury, poisoning and procedural complications
Fall	0/198 (0%)		0/201 (0%)		10/162 (6.2%)		10/160 (6.3%)
Investigations
Alanine aminotransferase increased	39/198 (19.7%)		53/201 (26.4%)		13/162 (8%)		11/160 (6.9%)
Aspartate aminotransferase increased	30/198 (15.2%)		41/201 (20.4%)		10/162 (6.2%)		9/160 (5.6%)
Blood creatinine increased	18/198 (9.1%)		13/201 (6.5%)		20/162 (12.3%)		13/160 (8.1%)
Electrocardiogram QT prolonged	21/198 (10.6%)		20/201 (10%)		20/162 (12.3%)		19/160 (11.9%)
Gamma-glutamyltransferase increased	12/198 (6.1%)		22/201 (10.9%)		10/162 (6.2%)		8/160 (5%)
Neutrophil count decreased	56/198 (28.3%)		49/201 (24.4%)		22/162 (13.6%)		22/160 (13.8%)
Platelet count decreased	77/198 (38.9%)		73/201 (36.3%)		30/162 (18.5%)		26/160 (16.3%)
Weight decreased	21/198 (10.6%)		22/201 (10.9%)		34/162 (21%)		19/160 (11.9%)
White blood cell count decreased	63/198 (31.8%)		53/201 (26.4%)		17/162 (10.5%)		18/160 (11.3%)
Blood alkaline phosphatase increased	14/198 (7.1%)		13/201 (6.5%)		0/162 (0%)		0/160 (0%)
Blood bilirubin increased	25/198 (12.6%)		13/201 (6.5%)		0/162 (0%)		0/160 (0%)
Lymphocyte count decreased	19/198 (9.6%)		21/201 (10.4%)		0/162 (0%)		0/160 (0%)
C-reactive protein increased	0/198 (0%)		0/201 (0%)		7/162 (4.3%)		9/160 (5.6%)
Metabolism and nutrition disorders
Decreased appetite	52/198 (26.3%)		41/201 (20.4%)		45/162 (27.8%)		21/160 (13.1%)
Hyperglycaemia	10/198 (5.1%)		10/201 (5%)		5/162 (3.1%)		9/160 (5.6%)
Hypoalbuminaemia	32/198 (16.2%)		30/201 (14.9%)		11/162 (6.8%)		13/160 (8.1%)
Hypocalcaemia	25/198 (12.6%)		17/201 (8.5%)		10/162 (6.2%)		13/160 (8.1%)
Hypokalaemia	76/198 (38.4%)		83/201 (41.3%)		35/162 (21.6%)		22/160 (13.8%)
Hypomagnesaemia	29/198 (14.6%)		24/201 (11.9%)		11/162 (6.8%)		5/160 (3.1%)
Hyponatraemia	24/198 (12.1%)		15/201 (7.5%)		16/162 (9.9%)		9/160 (5.6%)
Hypophosphataemia	42/198 (21.2%)		44/201 (21.9%)		10/162 (6.2%)		15/160 (9.4%)
Hyperuricaemia	13/198 (6.6%)		9/201 (4.5%)		0/162 (0%)		0/160 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	17/198 (8.6%)		14/201 (7%)		11/162 (6.8%)		11/160 (6.9%)
Back pain	22/198 (11.1%)		17/201 (8.5%)		7/162 (4.3%)		12/160 (7.5%)
Muscle spasms	20/198 (10.1%)		3/201 (1.5%)		28/162 (17.3%)		4/160 (2.5%)
Myalgia	15/198 (7.6%)		11/201 (5.5%)		0/162 (0%)		0/160 (0%)
Nervous system disorders
Dizziness	23/198 (11.6%)		18/201 (9%)		9/162 (5.6%)		14/160 (8.8%)
Dysgeusia	39/198 (19.7%)		20/201 (10%)		37/162 (22.8%)		8/160 (5%)
Headache	39/198 (19.7%)		47/201 (23.4%)		4/162 (2.5%)		9/160 (5.6%)
Paraesthesia	11/198 (5.6%)		0/201 (0%)		0/162 (0%)		0/160 (0%)
Psychiatric disorders
Insomnia	27/198 (13.6%)		30/201 (14.9%)		12/162 (7.4%)		8/160 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	23/198 (11.6%)		23/201 (11.4%)		10/162 (6.2%)		20/160 (12.5%)
Dyspnoea	15/198 (7.6%)		23/201 (11.4%)		11/162 (6.8%)		18/160 (11.3%)
Epistaxis	19/198 (9.6%)		20/201 (10%)		8/162 (4.9%)		10/160 (6.3%)
Oropharyngeal pain	19/198 (9.6%)		19/201 (9.5%)		0/162 (0%)		0/160 (0%)
Skin and subcutaneous tissue disorders
Alopecia	22/198 (11.1%)		26/201 (12.9%)		20/162 (12.3%)		3/160 (1.9%)
Pruritus	12/198 (6.1%)		11/201 (5.5%)		8/162 (4.9%)		9/160 (5.6%)
Rash	46/198 (23.2%)		51/201 (25.4%)		10/162 (6.2%)		13/160 (8.1%)
Dry skin	13/198 (6.6%)		10/201 (5%)		0/162 (0%)		0/160 (0%)
Petechiae	8/198 (4%)		11/201 (5.5%)		0/162 (0%)		0/160 (0%)
Rash maculo-papular	21/198 (10.6%)		21/201 (10.4%)		0/162 (0%)		0/160 (0%)
Vascular disorders
Hypertension	10/198 (5.1%)		25/201 (12.4%)		0/162 (0%)		0/160 (0%)
Hypotension	18/198 (9.1%)		17/201 (8.5%)		0/162 (0%)		0/160 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.