A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy
A Phase 3 Multicenter, Open-label, Randomized Study of ASP2215 (Gilteritinib), Combination of ASP2215 Plus Azacitidine and Azacitidine Alone in the Treatment of Newly Diagnosed Acute Myeloid Leukemia With FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy
2 other identifiers
interventional
183
13 countries
111
Brief Summary
This was a clinical study for adult participants who were recently diagnosed with acute myeloid leukemia or AML. AML is a type of cancer. It is when bone marrow makes white blood cells that are not normal. These are called leukemia cells. Some participants with AML have a mutation, or change, in the FLT3 gene. This gene helps leukemia cells make a protein called FLT3. This protein causes the leukemia cells to grow faster. For participants with AML who could not receive standard chemotherapy, azacitidine (also known as Vidaza®) was a current standard of care treatment option in the United States. This clinical study tested an experimental medicine called ASP2215, also known as gilteritinib. Gilteritinib worked by stopping the leukemia cells from making the FLT3 protein. This helped stop the leukemia cells from growing faster. This study compared two different treatments. Participants were assigned to one of these two groups by chance: a medicine called azacitidine, also known as Vidaza®, or an experimental medicine gilteritinib in combination with azacitidine. There was a twice as much chance to receive both medicines combined than azacitidine alone. The clinical study may help show which treatment helps patients live longer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Aug 2016
Longer than P75 for phase_3
111 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 22, 2016
CompletedFirst Posted
Study publicly available on registry
April 26, 2016
CompletedStudy Start
First participant enrolled
August 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 10, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2024
CompletedResults Posted
Study results publicly available
September 12, 2025
CompletedSeptember 12, 2025
August 1, 2025
6.6 years
April 22, 2016
July 16, 2025
August 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
OS was defined as the time from the date of randomization until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. Kaplan-Meier (KM) estimates was used for analysis.
From the date of randomization until the date of death from any cause ( maximum duration up to 79 months)
Secondary Outcomes (13)
Event-free Survival (EFS)
From the date of randomization until the date of documented relapse from CR, treatment failure or death from any cause, whichever occurred first (up to 39.7 months)
Percentage of Participants With Best Response
From the date of randomization until the date of death from any cause (up to 57 months)
Completed Remission (CR) Rate
From the date of randomization until the date of death from any cause (approximately 49.7 months)
CRc Rate
From the date of randomization until the date of death from any cause (approximately 54.5 months)
Complete Remission With Partial Hematologic Recovery (CRh)
From the date of randomization until the date of death from any cause (up to 49.7 months)
- +8 more secondary outcomes
Study Arms (4)
Safety Cohort: Gilteritinib + Azacitidine (AZA)
EXPERIMENTALParticipants received 80 mg (2 tablets of 40 mg) of gilteritinib orally once daily for continuous 28-day cycles and 75 mg/m\^2 of AZA daily via subcutaneous injection or intravenous infusion for 7 days of each 28-day treatment cycle. Depending on the safety cohort data ,the decision to initiate the randomized trial at the targeted dose was made. After the end of treatment period, participants were followed up for 30- day follow up period. Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death). Participants in long-term follow-up who were no longer receiving treatment were followed every 3 months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study, as further survival data were no longer needed.
Randomized Cohort: Gilteritinib + AZA
EXPERIMENTALParticipants received 120 mg(3 tablets of 40 mg)of gilteritinib orally once daily for continuous 28-day cycles in combination with 75mg/m\^2 of AZA daily via subcutaneous injection or IV infusion for 7days of each 28-day treatment cycle until the participant no longer received clinical benefit from therapy in the opinion of the investigator,unacceptable toxicity occurred,or the participant met another treatment discontinuation criterion.After the end of treatment period,participants were followed up for 30-day follow up period.Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment,EQ-5D-5L,remission status and survival (cause and date of death).Participants in long-term follow-up who were no longer receiving treatment were followed every 3months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study,as further survival data were no longer needed.
Randomized Cohort: AZA
EXPERIMENTALParticipants received 75 mg/m\^2 of AZA daily via subcutaneous injection or intravenous infusion for 7 days of each 28-day treatment cycle until the participant no longer received clinical benefit from therapy in the opinion of the investigator, unacceptable toxicity occurred or the participant met another treatment discontinuation criterion. After the end of treatment period, participants were followed up for 30- day follow up period. Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death). Participants in long-term follow-up who were no longer receiving treatment were followed every 3 months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study, as further survival data were no longer needed.
Randomized Cohort: Gilteritinib
ACTIVE COMPARATORParticipants received 120 mg (3 tablets of 40 mg) of gilteritinib orally once daily for continuous 28-day cycles until the participant no longer received clinical benefit from therapy in the opinion of the investigator, unacceptable toxicity occurred or the participant met another treatment discontinuation criterion. However, randomization to this arm was removed in protocol version 7.0. Participants previously randomized to this arm continued following treatment and assessments as outlined in the protocol.
Interventions
Tablet, oral
Subcutaneous injection or intravenous infusion
Eligibility Criteria
You may qualify if:
- Subject is considered an adult according to local regulation at the time of obtaining informed consent.
- Subject has a diagnosis of previously-untreated AML according to World Health Organization (WHO) classification \[Swerdlow et al, 2008\] as determined by pathology review at the treating institution.
- Subject is positive for FLT3 mutation (internal tandem duplication \[ITD\] or tyrosine kinase domain \[TKD\] \[D835/I836\] mutation) (or for Korea only: ITD alone or ITD with concurrent TKD activating mutation) in bone marrow or whole blood as determined by central laboratory. Note: Only requirement of FLT3 mutation assessment by central laboratory is only applicable to the randomization portion of the study.
- Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:
- Subject is ≥ 65 years of age and ineligible for intensive induction chemotherapy.
- Subject is ≥ 18 to 64 years of age and has any of the following comorbidities: \[Ex-US Only\]: Congestive heart failure (New York Heart Association {NYHA} class ≤ 3) or ejection fraction (Ef) ≤ 50%; \[US Only\]: Severe cardiac disorder e.g. congestive heart failure (New York Heart Association \[NYHA\] class ≤ 3) requiring treatment, ejection fraction ≤ 50%, or chronic stable angina; \[Ex-US Only\]: Creatinine \> 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; \[US Only\]: Creatinine clearance \< 45 mL/min; ECOG performance status ≥ 2;
- \[Ex-US Only\]: Known pulmonary disease with decreased diffusion capacity of lung for carbon monoxide (DLCO) and/or requiring oxygen ≤ 2 liters per minute; \[US Only\] Severe pulmonary disorder (e.g., diffusion capacity of lung for carbon monoxide \[DLCO\] ≤ 65% or forced expiratory volume in the first second \[FEV1\] ≤ 65%); Prior or current malignancy that does not require concurrent treatment; Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of another anthracycline). Any other comorbidity incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and before randomization.
- Subject must meet the following criteria as indicated on the clinical laboratory tests:
- Serum AST and ALT ≤ 3.0 x Institutional upper limit of normal (ULN)
- Serum total bilirubin ≤ 1.5 x Institutional ULN
- Serum potassium ≥ Institutional lower limit of normal (LLN)
- Serum magnesium ≥ Institutional LLN Repletion of potassium and magnesium levels during the screening period is allowed.
- Subject is suitable for oral administration of study drug.
- Female subject is eligible to participate if female subject is not pregnant and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP); OR
- +6 more criteria
You may not qualify if:
- Subject was diagnosed as acute promyelocytic leukemia (APL).
- Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Subject has received previous therapy for AML, with the exception of the following:
- Emergency leukapheresis
- Hydroxyurea
- Growth factor or cytokine support
- Steroids
- Subject has clinically active central nervous system leukemia.
- Subject has been diagnosed with another malignancy that requires concurrent treatment (with the exception of hormone therapy limited to those therapies that prevent recurrence and/or spread of cancer) or hepatic malignancy regardless of need for treatment.
- Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 CYP3A/P-glycoprotein (P-gp).
- Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the subject.
- Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
- Subject has congestive heart failure classified as New York Heart Association Class IV.
- Subject with mean Fridericia-corrected QT interval (QTcF) \> 480 ms at screening based on central reading.
- Subject with a history of Long QT Syndrome at screening.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (111)
UCLA David Geffen School of Medicine
Los Angeles, California, 90095, United States
University of California, Irvine Medical Center
Orange, California, 92868, United States
Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, 60611-5975, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
St. Louis University Cancer Center - Hematology/Oncology
St Louis, Missouri, 63110, United States
Hackensack University Medical Center - John Theurer Cancer Center
Hackensack, New Jersey, 07601, United States
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, 07962, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021, United States
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, 10021, United States
GHS Cancer Institute
Greenville, South Carolina, 26615, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
Site AU61004
Liverpool, New South Wales, 2170, Australia
Site AU61008
Adelaide, South Australia, SA 5000, Australia
Site AU61007
Geelong, Victoria, 3220, Australia
Site BE32007
Brussels, Brussels Capital, 1090, Belgium
Site BE32003
Brussels, Bruxelles-Capitale, Region de, 1200, Belgium
Site BE32006
Ghent, 9000, Belgium
Site CA15009
Edmonton, Alberta, T6G 2B7, Canada
Site CA15011
Toronto, Ontario, M4N 3M5, Canada
Site CA15002
Toronto, Ontario, M5G 2M9, Canada
Site CA15006
Montreal, Quebec, H4A 3J1, Canada
Site FR33003
Nîmes, Gard, 30029, France
Site FR33002
Pessac, Gironde, 33604, France
Site FR33015
Rouen, Haute-Normandie, 76038, France
Site FR33019
Montpellier, Herault, 34295, France
Site FR33018
Rennes, Ille-et-Vilaine, 35033, France
Site FR33001
Nantes, Loire-Atlantique, 44093, France
Site FR33023
Valenciennes, Nord, 59322, France
Site FR33013
Pierre-Bénite, Rhone, 69310, France
Site FR33017
Le Mans, Sarthe, 72037, France
Site FR33012
Poitiers, Vienne, 86000, France
Site FR33009
Angers, 49033, France
Site FR33020
Bayonne, France
Site FR33004
Lille, 59020, France
Site FR33006
Lille, 59037, France
Site DE49002
Tübingen, Baden-Wurttemberg, 72076, Germany
Site DE49007
München, Bavaria, 81737, Germany
Site DE49005
Frankfurt am Main, Hesse, 60590, Germany
Site DE49012
Braunschweig, Lower Saxony, 38118, Germany
Site DE49004
Hanover, Lower Saxony, 30625, Germany
Site DE49015
Rostock, Mecklenburg-Vorpommern, 18057, Germany
Site DE49009
Halle, Saxony-Anhalt, 06120, Germany
Site DE49003
Berlin, 13353, Germany
Site DE49011
Stuttgart, 70376, Germany
Site IT39009
Ancona, 60126, Italy
Site IT39015
Bologna, 40138, Italy
Site IT39012
Florence, Italy
Site IT39004
Milan, 20162, Italy
Site IT39007
Monza, Italy
Site IT39001
Napoli, 80131, Italy
Site IT39014
Novara, Italy
Site IT39006
Palermo, 90146, Italy
Site IT39005
Pavia, Italy
Site IT39011
San Giovanni Rotondo, 71013, Italy
Site JP81018
Anjo, Aichi-ken, Japan
Site JP81007
Nagoya, Aichi-ken, Japan
Site JP81027
Matsuyama, Ehime, Japan
Site JP81021
Fukuyama, Hiroshima, Japan
Site JP81031
Sapporo, Hokkaido, Japan
Site JP81033
Sapporo, Hokkaido, Japan
Site JP81015
Kobe, Hyōgo, Japan
Site JP81034
Hitachi, Ibaraki, Japan
Site JP81023
Kanazawa, Ishikawa-ken, Japan
Site JP81001
Isehara, Kanagawa, Japan
Site JP81032
Yokohama, Kanagawa, Japan
Site JP81012
Sendai, Miyagi, Japan
Site JP81011
Kurashiki, Okayama-ken, Japan
Site JP81029
Shibuya-ku, Tokyo, Japan
Site JP81014
Shinagawa-ku, Tokyo, Japan
Site JP81035
Chiba, Japan
Site JP81008
Fukuoka, Japan
Site JP81024
Gifu, Japan
Site JP81005
Kumamoto, Japan
Site JP81016
Kyoto, Japan
Site JP81004
Nagasaki, Japan
Site JP81017
Nagasaki, Japan
Site JP81030
Osaka, Japan
Site JP81036
Osaka, Japan
Site JP81026
Tokushima, Japan
Site JP81019
Toyama, Japan
Site PL48003
Lublin, Lublin Voivodeship, 20-081, Poland
Site PL48004
Warsaw, Masovian Voivodeship, 02-776, Poland
Site PL48002
Opole, Opole Voivodeship, 45-061, Poland
Site PL48001
Olsztyn, Warmian-Masurian Voivodeship, 10-228, Poland
Site KR82003
Namdong, Incheon Gwang'yeogsiv, 405 760, South Korea
Site KR82013
Seoul, Seoul Teugbyeolsi, 05505, South Korea
Site KR82006
Seoul, Seoul Teugbyeolsi, 110-744, South Korea
Site KR82002
Seoul, Seoul Teugbyeolsi, 137-701, South Korea
Site KR82001
Ulsan, Ulsan Gwang'yeogsi, 682-714, South Korea
Site KR82014
Busan, 49241, South Korea
Site KR82010
Hwasun-gun, South Korea
Site KR82015
Seongnam-si, South Korea
Site KR82012
Seoul, 156-707, South Korea
Site ES34007
Palma de Mallorca, Balearic Islands, 07010, Spain
Site ES34003
Oviedo, Principality of Asturias, 33011, Spain
Site ES34008
Barcelona, 08003, Spain
Site ES34004
Barcelona, 08035, Spain
Site ES34010
Barcelona, 08036, Spain
Site ES34009
Barcelona, 8041, Spain
Site ES34002
Cáceres, 10003, Spain
Site ES34013
Madrid, Spain
Site ES34005
Valencia, 46026, Spain
Site TW88604
Kaohsiung City, 83301, Taiwan
Site TW88605
Kwei Shan Hsiang, Taiwan
Site TW88602
Tainan, 704, Taiwan
Site TW88609
Tainan, 736, Taiwan
Site TW88601
Taipei, 10002, Taiwan
Site TW88608
Taipei, 10449, Taiwan
Site TW88610
Taipei, 11217, Taiwan
Site GB44007
Sheffield, S10 2JF, United Kingdom
Related Publications (1)
Wang ES, Montesinos P, Minden MD, Lee JH, Heuser M, Naoe T, Chou WC, Laribi K, Esteve J, Altman JK, Havelange V, Watson AM, Gambacorti-Passerini C, Patkowska E, Liu S, Wu R, Philipose N, Hill JE, Gill SC, Rich ES, Tiu RV. Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy. Blood. 2022 Oct 27;140(17):1845-1857. doi: 10.1182/blood.2021014586.
PMID: 35917453DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Protocol versions 6.0 and earlier included a 1:1:1 randomization ratio to receive Gilteritinib + AZA, AZA-only and Gilteritinib-only. Randomization to arm Gilteritinib-only was removed in protocol version 7.0. Participants previously randomized to Gilteritinib-only arm continued following treatment and assessments as outlined in the protocol.
Results Point of Contact
- Title
- Clinical Transparency
- Organization
- Astellas Pharma Global Development, Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Global Development, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
April 22, 2016
First Posted
April 26, 2016
Study Start
August 1, 2016
Primary Completion
March 10, 2023
Study Completion
December 18, 2024
Last Updated
September 12, 2025
Results First Posted
September 12, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.