A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia
NCT03416179
ABOUT THIS STUDY
FOR MORE INFORMATION
Contact a representative by phone, email, or visiting the study website. Please see the references below:
Pfizer Clinical Trials Contact Center
1-800-718-1021
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the Intensive and Non Intensive study (unless where indicated):
1. Subjects with untreated AML according to the World Health Organization (WHO) 2016 Classification2, including those with:
- AML arising from MDS or another antecedent hematologic disease (AHD).
- AML after previous cytotoxic therapy or radiation (secondary AML).
2. 18 years of age (In Japan, 20 years of age).
3. Adequate Organ Function as defined by the following:
- Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) 3 x upper limit of normal (ULN), excluding subjects with liver function abnormalities due to underlying malignancy.
- Total serum bilirubin 2 x ULN (except subjects with documented Gilbert's syndrome).
- Estimated creatinine clearance 30 mL/min as calculated using the standard method for the institution.
4. QTc interval 470 msec using the Fridericia correction (QTcF).
5. All anti cancer treatments (unless specified) should be discontinued 2 weeks from study entry, for example: targeted chemotherapy, radiotherapy, investigational agents, hormones, anagrelide or cytokines.
- For control of rapidly progressing leukemia, all trans retinoic acid (ATRA), hydroxyurea, and/or leukopheresis may be used before and for up to 1 week after the first dose of glasdegib.
6. Serum or urine pregnancy test (for female subjects of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (hCG) negative at screening.
7. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use at least one highly effective method of contraception throughout the study and for 180 days after the last dose of azacitidine, cytarabine, or daunorubicin; and the last dose of glasdegib or placebo, whichever occurs later.
8. Female subjects of non childbearing potential must meet at least 1 of the following criteria:
1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
2. Have medically confirmed ovarian failure; or
3. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
9. Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
10. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
11. Subjects who are willing and able to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow [BM] assessments).
Subjects with any of the following characteristics/conditions will not be included in the
study:
1. Acute Promyelocytic Leukemia (APL) and APLwith PML RARA, subjects (WHO 2016
classification).
2. AML with BCR ABL1 or t(9;22)(q34;q11.2) as a sole abnormality.
- Complex genetics may include t(9;22) cytogenetic translocation.
3. Subjects with known active CNS leukemia.
4. Participation in other clinical studies involving other investigational drug(s)
(Phases 1 4) within 4 weeks prior study entry and/or during study participation.
5. Subjects known to be refractory to platelet or packed red cell transfusions per
Institutional Guidelines, or a patient who refuses blood product support.
6. Subjects with another active malignancy on treatment with the exception of basal cell
carcinoma, non melanoma skin cancer, cervical carcinoma in situ. Other prior or
concurrent malignancies will be considered on a case by case basis.
7. Any one of the following ongoing or in the previous 6 months: myocardial infarction,
congenital long QT syndrome, Torsades de pointes, symptomatic arrhythmias (including
sustained ventricular tachyarrhythmia), right or left bundle branch block and
bifascicular block, unstable angina, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure (CHF New York Heart Association class III or IV),
cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism;
as well as bradycardia defined as <50 bpms.
8. Subjects with an active, life threatening or clinically significant uncontrolled
systemic infection not related to AML.
9. Subjects with left ventricular ejection fraction (LVEF) <50% are excluded from the
Intensive Chemotherapy Study only.
10. Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the
Intensive Chemotherapy Study only.
11. Known malabsorption syndrome or other condition that may significantly impair
absorption of study medication in the investigator's judgment (eg, gastrectomy, lap
band, Crohn's disease) and inability or unwillingness to swallow tablets or capsules.
12. Current use or anticipated requirement for drugs that are known strong CYP3A4/5
inducers.
13. Concurrent administration of herbal preparations.
14. Major surgery or radiation within 4 weeks of starting study treatment.
15. Documented or suspected hypersensitivity to any one of the following:
- For subjects assigned to intensive chemotherapy, documented or suspected
hypersensitivity to cytarabine (not including drug fever or exanthema, including
known cerebellar side effects) or daunorubicin.
- For subjects assigned to non intensive chemotherapy, documented or suspected
hypersensitivity to azacitidine or mannitol.
16. Known active drug or alcohol abuse.
17. Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the subject inappropriate for entry into this
study.
18. Pregnant females or breastfeeding female subjects.
19. Known recent or active suicidal ideation or behavior.
20. Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
subjects who are Pfizer employees, including their family members, directly involved
in the conduct of the study.
NEED INFO?
Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

TRY A NEW SEARCH
Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.
Based on your search, you may also be interested in
- Memphis, Tennessee
- New York, New York
- Munich, Bavaria
- Los Angeles, California
- Los Angeles, California
- Los Angeles, California
- Los Angeles, California
- Los Angeles, California
- Orange, California
- Orange, California
- San Francisco, California
- San Francisco, California
- San Francisco, California
- Westlake Village, California
- Augusta, Georgia
- Augusta, Georgia
- Augusta, Georgia
- Boston, Massachusetts
- Boston, Massachusetts
- Boston, Massachusetts
- Kansas City, Missouri
- Lake Success, New York
- Manhasset, New York
- New Hyde Park, New York
- Rochester, New York
- Rochester, New York
- Cleveland, Ohio
- Cleveland, Ohio
- Cleveland, Ohio
- Portland, Oregon
- Portland, Oregon
- Portland, Oregon
- Nashville, Tennessee
- Nashville, Tennessee
- Dallas, Texas
- Dallas, Texas
- San Antonio, Texas
- San Antonio, Texas
- San Antonio, Texas
- Seattle, Washington
- Seattle, Washington
- Seattle, Washington
- Darlinghurst, New South Wales
- Kogarah, New South Wales
- Adelaide, South Australia
- Adelaide, South Australia
- Salzburg,
- Salzburg,
- Wien,
- Wien,
- Brugge,
- Brussels,
- Brussels,
- Leuven,
- Winnipeg, Manitoba
- Winnipeg, Manitoba
- Toronto, Ontario
- Toronto, Ontario
- Montreal, Quebec
- Saskatoon, Saskatchewan
- Saskatoon, Saskatchewan
- Hefei, Anhui
- Hefei, Anhui
- Fuzhou, Fujian
- Guangzhou, Guangdong
- Guangzhou, Guangdong
- Langfang, Hebei
- Zhengzhou, Henan
- Zhengzhou, Henan
- Wuhan, Hubei
- Chengdu, Sichuan
- Tianjin, Tianjin
- Hangzhou, Zhejiang
- Shanghai,
- Brno,
- Brno,
- Ostrava - Poruba,
- Ostrava-Poruba,
- Praha 10,
- Praha 10,
- Creteil,
- Créteil,
- Nantes cedex 1,
- Nantes cedex,
- Paris,
- Pierre Benite cedex,
- Pierre Benite cedex,
- Villejuif cedex,
- Marburg, Hesse
- Koeln, North Rhine Westphalia
- Muenster, North Rhine-westphalia
- Muenster, North-rhine-westphalia
- Hamburg,
- Hannover,
- Debrecen,
- Debrecen,
- Győr,
- Győr,
- Kaposvar,
- Nyiregyhaza,
- Nyiregyhaza,
- Haifa,
- Jerusalem,
- Jerusalem,
- Petah Tikva,
- Petah Tikva,
- Torrette Di Ancona, Ancona
- Torette Di Ancona, AN
- Cona, Ferrara, FE
- Ferrara, FE
- Pesaro, PU
- Siena, SI
- Bologna,
- Siena,
- Nagoya, Aichi
- Yoshida-gun, Fukui
- Maebashi, Gunma
- Kobe-shi, Hyogo
- Yokohama, Kanagawa
- Sendai, Miyagi
- Osaka-City, Osaka
- Osaka-Sayama, Osaka
- Sunto-gun, Shizuoka
- Tachikawa, Tokyo
- Akita,
- Fukuoka,
- Kumamoto,
- Nagasaki,
- Tokyo,
- Jeonju-si, Jeollabuk-do
- Busan,
- Busan,
- Daegu,
- Daegu,
- Incheon,
- Seoul,
- Seoul,
- Seoul,
- Seoul,
- Seoul,
- Seoul,
- Seoul,
- Seoul,
- México, MÉX
- Monterrey, Nuevo LEON
- Gdansk,
- Lodz,
- Cluj-Napoca, Cluj
- Craiova, Dolj
- Bucuresti,
- Bucuresti,
- Moscow,
- Moscow,
- Nizhniy Novgorod,
- Ryazan,
- Saint Petersburg,
- Saint Petersburg,
- Barcelona,
- Barcelona,
- Lleida,
- Madrid,
- Madrid,
- Sevilla,
- Valencia,
- Orebro,
- Orebro,
- Solna,
- Stockholm,
- Tainan,
- Taipei,
- Taipei,
- Taipei,
- Taipei,
- Taipei,
- Taoyuan City,
- Taoyuan City,
- Sutton, Surrey
- Birmingham, WEST Midlands
- Birmingham, WEST Midlands
- London,
Descriptive Information | |||||||
---|---|---|---|---|---|---|---|
Brief Title ICMJE | A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia | ||||||
Official Title ICMJE | 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 | ||||||
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). | ||||||
Detailed Description | Two separate registration trials conducted under one protocol number are proposed to adequately and independently evaluate the addition of glasdegib in intensive and non-intensive chemotherapy populations. Each study will have an experimental treatment arm and a placebo arm. Endpoints are the same for each study except where specifically indicated. Assignment to the Intensive Study or the Non-Intensive Study will be made by the Investigator based on the 2017 European LeukemiaNet (ELN) recommendations. Study B1371019 is a randomized (1:1), double-blind, multi-center, placebo controlled study of chemotherapy in combination with glasdegib versus chemotherapy in combination with placebo in adult patients with previously untreated AML. Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population). Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population). | ||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 3 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Randomized, double-blind, multi-center, placebo controlled study. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Double blind study. Primary Purpose: Treatment
| ||||||
Condition ICMJE | Leukemia, Myeloid, Acute | ||||||
Intervention ICMJE |
| ||||||
Study Arms ICMJE |
| ||||||
Publications * | Cortes JE, Dombret H, Merchant A, Tauchi T, DiRienzo CG, Sleight B, Zhang X, Leip EP, Shaik N, Bell T, Chan G, Sekeres MA. Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. Future Oncol. 2019 Nov;15(31):3531-3545. doi: 10.2217/fon-2019-0373. Epub 2019 Sep 13. | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | |||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||
Actual Enrollment ICMJE | 731 | ||||||
Original Estimated Enrollment ICMJE | 720 | ||||||
Estimated Study Completion Date ICMJE | December 13, 2022 | ||||||
Actual Primary Completion Date | June 5, 2020 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | 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):
Exclusion Criteria: Subjects with any of the following characteristics/conditions will not be included in the study:
| ||||||
Sex/Gender ICMJE |
| ||||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Australia, Austria, Belgium, Canada, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States | ||||||
Removed Location Countries | Greece | ||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03416179 | ||||||
Other Study ID Numbers ICMJE | B1371019 2017-002822-19 ( EudraCT Number ) BRIGHT ( Other Identifier: Alias Study Number ) BRIGHT AML1019 ( Other Identifier: Alias Study Number ) | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
| ||||||
IPD Sharing Statement ICMJE |
| ||||||
Responsible Party | Pfizer | ||||||
Study Sponsor ICMJE | Pfizer | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
| ||||||
PRS Account | Pfizer | ||||||
Verification Date | March 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |