A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
A Phase 3 Open-Label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation
2 other identifiers
interventional
371
14 countries
126
Brief Summary
The purpose of this study was to determine the clinical benefit of ASP2215 therapy in participants with FMS-like tyrosine kinase (FLT3) mutated acute myeloid leukemia (AML) who were refractory to or had relapsed after first-line AML therapy as shown with overall survival (OS) compared to salvage chemotherapy, and determined the efficacy of ASP2215 therapy as assessed by the rate of complete remission and complete remission with partial hematological recovery (CR/CRh) in these participants. This study also determined the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2015
Longer than P75 for phase_3
126 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 16, 2015
CompletedFirst Posted
Study publicly available on registry
April 21, 2015
CompletedStudy Start
First participant enrolled
October 20, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 17, 2018
CompletedResults Posted
Study results publicly available
October 17, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 25, 2025
CompletedDecember 4, 2025
November 1, 2025
2.9 years
April 16, 2015
September 12, 2019
November 27, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Duration of Overall Survival (OS)
Overall survival was defined as the time from the date of randomization until the date of death from any cause (death date - randomization date + 1). 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 (date of last contact - randomized date + 1). The date of last contact was the latest date that the participant was known to be alive. The last contact date was derived for participants alive at the analysis cutoff date. Survival rate and 95% CI were estimated using the Kaplan-Meier method and the Greenwood formula.
From randomization to until the date of death from any cause (median time of follow-up for OS was 17.8 months)
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm
The CR/CRh rate was defined as the number of participants who achieved either CR or CRh divided by the number of participants in the analysis population. CR: For participants to be classified as being in CR at, they must have had bone marrow regenerating normal hematopoietic cells and achieved a morphologic leukemia-free state and must had an ANC ≥ 1 x 10\^9/L and platelet count ≥ 100 x 10\^9/L and normal marrow differential with \< 5% blasts, and they were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There was no evidence of extramedullary leukemia. CRh: Participants were classified as CRh if they had marrow blasts \< 5%, partial hematologic recovery ANC ≥ 0.5 x 10\^9/L and platelets ≥ 50 x 10\^9/L, no evidence of extramedullary leukemia and could not be classified as CR.
From the date of randomization up to at least 112 days
Secondary Outcomes (10)
Duration of Event-Free Survival (EFS)
From the date of randomization until the date of documented relapse, treatment failure or death from any cause (median time of follow-up was 17.8 months)
Percentage of Participants With Complete Remission (CR) Rate
From the date of randomization up to at least 6 months
Duration of Leukemia-Free Survival (LFS)
From the date of first CRc until the date of documented relapse or death for participants who achieved CRc (median time of follow-up was 17.8 months)
Duration of Remission
From the date of first response until the date of documented relapse for participants who achieved CRc or PR (median time of follow-up was 17.8 months)
Percentage of Participants With Composite Complete Remission (CRc Rate)
From the date of randomization up to at least 6 months
- +5 more secondary outcomes
Study Arms (2)
Gilteritinib
EXPERIMENTALParticipants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Salvage Chemotherapy
ACTIVE COMPARATORParticipants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m\^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m\^2 daily by IV for 5 days, etoposide 100 mg/m\^2 daily by IV for 5 days and cytarabine 1000 mg/m\^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m\^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m\^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m\^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m\^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Interventions
SC (G-CSF) and IV (Fludarabine, Cytarabine, Idarubicin) injection
Eligibility Criteria
You may qualify if:
- Participant has a diagnosis of primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) according to WHO classification (2008) as determined by pathology review at the treating institute.
- Participant is refractory to or relapsed after first-line AML therapy (with or without hematopoietic stem cell transplant (HSCT)).
- Refractory to first-line AML therapy is defined as:
- \. Participant did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A Participant eligible for standard therapy must receive at least one cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A Participant not eligible for standard therapy must have received at least one complete block of induction therapy seen as the optimum choice of therapy to induce remission for this subject.
- Untreated first hematologic relapse is defined as:
- Participant must have achieved a CR/CRi/CRp (criteria as defined by \[Cheson et al, 2003\], see Section 5.3) with first line treatment and has hematologic relapse.
- Participant is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab. A Participant with rapidly proliferative disease and unable to wait for the central lab results can be enrolled based on a local test performed after completion of the last interventional treatment. Participants can be enrolled from a local test result if they have any of the following FLT3 mutations: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD)/D835 or FLT3- TKD/I836.
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Participant is eligible for pre-selected salvage chemotherapy.
- Participant must meet the following criteria as indicated on the clinical laboratory tests:
- Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN)
- Serum total bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of \> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
- Participant is suitable for oral administration of study drug.
- Female Participant must either:
- +12 more criteria
You may not qualify if:
- Participant was diagnosed as acute promyelocytic leukemia (APL).
- Participant has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Participant has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
- Participant is in second or later hematologic relapse or has received salvage therapy for refractory disease
- Participant has clinically active central nervous system leukemia.
- Participant has been diagnosed with another malignancy, unless disease-free for at least 5 years. Participants with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
- Participant has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation, and/or maintenance).
- Participant has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).
- Participant has had major surgery within 4 weeks prior to the first study dose.
- Participant has radiation therapy within 4 weeks prior to the first study dose.
- Participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or Participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
- Participant requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A.
- Participants with mean of triplicate Fridericia-corrected QT interval (QTcF) \> 450 ms at Screening based on central reading.
- Participants with Long QT Syndrome at Screening.
- Participants with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal \[LLN\]).
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (126)
Site US10011
Birmingham, Alabama, 35294-0006, United States
Site US10012
Los Angeles, California, 90095-1752, United States
Site US10076
Orange, California, 92868, United States
Site US10073
San Francisco, California, 94143, United States
Site US10067
New Haven, Connecticut, 06504, United States
Site US10045
Gainesville, Florida, 32610, United States
Site US10081
Atlanta, Georgia, 30342, United States
Site US10006
Chicago, Illinois, 60637, United States
Site US10075
Westwood, Kansas, 66205, United States
Site US10074
Louisville, Kentucky, 40202, United States
Site US10048
New Orleans, Louisiana, 70112, United States
Site US10005
Baltimore, Maryland, 21201, United States
Site US10034
Boston, Massachusetts, 02114, United States
Site US10022
Boston, Massachusetts, 02215, United States
Site US10085
Boston, Massachusetts, 02215, United States
Site US10087
Detroit, Michigan, 48201, United States
Site US10057
Minneapolis, Minnesota, 55455, United States
Site US10023
Lebanon, New Hampshire, 03756-1000, United States
Site US10027
Hackensack, New Jersey, 07601, United States
Site US10077
New Brunswick, New Jersey, 08903, United States
Site US10001
Buffalo, New York, 14263, United States
Site US10037
New York, New York, 10029, United States
Site US10008
New York, New York, 10032, United States
Site US10013
New York, New York, 10065, United States
Site US10072
New York, New York, 10065, United States
Site US10046
Syracuse, New York, 13210, United States
Site US10024
Durham, North Carolina, 27710, United States
Site US10078
Winston-Salem, North Carolina, 27157, United States
Site US10044
Cleveland, Ohio, 44106, United States
Site US10084
Columbus, Ohio, 43210, United States
Site US10058
Oklahoma City, Oklahoma, 73104, United States
Site US10041
Hershey, Pennsylvania, 17033, United States
Site US10010
Philadelphia, Pennsylvania, 19104, United States
Site US10080
Philadelphia, Pennsylvania, 19107, United States
Site US10014
Charleston, South Carolina, 29425, United States
Site US10063
Nashville, Tennessee, 37232-0656, United States
Site US10035
Milwaukee, Wisconsin, 53226, United States
Site BE32002
Yvoir, 5530, Belgium
Site CA15004
Edmonton, Alberta, T6G 2G3, Canada
Site CA15001
Hamilton, Ontario, L8V 1C3, Canada
Site CA15015
Toronto, Ontario, M5G 2M9, Canada
Site CA15003
Montreal, Quebec, H1T 2M4, Canada
Site FR33013
Brest, 29609, France
Site FR33002
Le Chesnay, 78157, France
Site FR33010
Lille, 59037, France
Site FR33009
Pessac, 33604, France
Site FR33014
Rennes, 35033, France
Site FR33008
Toulouse, 31059, France
Site DE49009
Dresden, 01307, Germany
Site DE49011
Leipzig, 04103, Germany
Site DE49003
Marburg, 35043, Germany
Site DE49002
München, 81737, Germany
Site DE49010
Tübingen, 72076, Germany
Site IL97201
Ashkelon, 78278, Israel
Site IL97209
Haifa, 31096, Israel
Site IL97203
Jerusalem, 91031, Israel
Site IL97210
Jerusalem, 91120, Israel
Site IL97206
Petah Tikva, 49100, Israel
Site IL97208
Rehovot, 76100, Israel
Site IT39005
Bologna, 40138, Italy
Site IT39010
Brescia, 25126, Italy
Site IT39001
Milan, 20132, Italy
Site IT39004
Palermo, 90146, Italy
Site IT39011
Pavia, 27100, Italy
Site IT39007
Roma, 00189, Italy
Site IT39002
Varese, 21100, Italy
Site JP81002
Nagoya, Aichi-ken, Japan
Site JP81010
Narita, Chiba, Japan
Site JP81026
Yoshida-gun, Fukui, Japan
Site JP81016
Sapporo, Hokkaido, Japan
Site JP81018
Kobe, Hyōgo, Japan
Site JP81017
Tsukuba, Ibaraki, Japan
Site JP81009
Isehara, Kanagawa, Japan
Site JP81006
Yokohama, Kanagawa, Japan
Site JP81012
Sendai, Miyagi, Japan
Site JP81007
Kurashiki, Okayama-ken, Japan
Site JP81014
Sayama, Osaka, Japan
Site JP81020
Kawagoe, Saitama, Japan
Site JP81027
Shimotsuke, Tochigi, Japan
Site JP81005
Chuo-ku, Tokyo, Japan
Site JP81004
Shinagawa-ku, Tokyo, Japan
Site JP81022
Shinjuku-ku, Tokyo, Japan
Site JP81023
Akita, Japan
Site JP81021
Aomori, Japan
Site JP81013
Kumamoto, Japan
Site JP81025
Kyoto, Japan
Site JP81008
Nagasaki, Japan
Site JP81024
Okayama, Japan
Site JP81011
Osaka, Japan
Site PL48002
Gdansk, 80-952, Poland
Site PL48005
Opole, 45-372, Poland
Site PL48004
Wroclaw, 50-367, Poland
Site KR82005
Suwon, Gyeonggi-do, 443380, South Korea
Site KR82010
Busan, 602739, South Korea
Site KR82009
Goyang, 602-715, South Korea
Site KR82003
Jeollanam-do, 519-809, South Korea
Site KR82007
Seoul, 110-744, South Korea
Site KR82004
Seoul, 120-752, South Korea
Site KR82001
Seoul, 135710, South Korea
Site KR82002
Seoul, 137701, South Korea
Site KR82008
Seoul, 138-736, South Korea
Site KR82011
Seoul, 156-707, South Korea
Site ES34009
Badalona, 08025, Spain
Site ES34011
Barcelona, 08035, Spain
Site ES34012
Barcelona, 08036, Spain
Site ES34010
Barcelona, 08916, Spain
Site ES34016
Girona, 17007, Spain
Site ES34005
L'Hospitalet de Llobregat, 08907, Spain
Site ES34014
Salamanca, 37007, Spain
Site ES34017
Valencia, 46026, Spain
Site TW88606
Kaohsiung City, 112, Taiwan
Site TW88604
Kaohsiung City, 83301, Taiwan
Site TW88608
Taichung, 404, Taiwan
Site TW88609
Taichung, 40705, Taiwan
Site TW88601
Tainan, 704, Taiwan
Site TW88603
Taipei, 10002, Taiwan
Site TW88610
Taipei, 10449, Taiwan
Site TW88611
Taipei, 112, Taiwan
Site TW88602
Taipei, 114, Taiwan
Site TW88605
Taoyuan District, 33305, Taiwan
Site TR90001
Ankara, 06100, Turkey (Türkiye)
Site TR90004
Ankara, 06500, Turkey (Türkiye)
Site GB44014
Bournemouth, BH7 7DW, United Kingdom
Site GB44013
Harrow, HA1 3UJ, United Kingdom
Site GB44003
Manchester, M13 9WL, United Kingdom
Site GB44015
Plymouth, PL6 8DH, United Kingdom
Related Publications (4)
Ritchie EK, Cella D, Fabbiano F, Pigneux A, Kanda Y, Ivanescu C, Pandya BJ, Shah MV. Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML. Leuk Lymphoma. 2023 May;64(5):938-950. doi: 10.1080/10428194.2023.2186731. Epub 2023 Apr 5.
PMID: 37019445DERIVEDSmith CC, Levis MJ, Perl AE, Hill JE, Rosales M, Bahceci E. Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv. 2022 Apr 12;6(7):2144-2155. doi: 10.1182/bloodadvances.2021006489.
PMID: 35130342DERIVEDPerl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Recher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. doi: 10.1182/blood.2021011583.
PMID: 35081255DERIVEDPerl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-1740. doi: 10.1056/NEJMoa1902688.
PMID: 31665578DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Global Development, Inc.
Study Officials
- STUDY DIRECTOR
Executive 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 16, 2015
First Posted
April 21, 2015
Study Start
October 20, 2015
Primary Completion
September 17, 2018
Study Completion
February 25, 2025
Last Updated
December 4, 2025
Results First Posted
October 17, 2019
Record last verified: 2025-11
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/.