A Trial of the FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/Internal Tandem Duplication (ITD) Acute Myeloid Leukemia (AML)
A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Trial of the FLT3 Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/ITD AML
3 other identifiers
interventional
356
16 countries
118
Brief Summary
The purpose of this study was to compare relapse-free survival between participants with FLT3/ITD AML in first morphologic complete remission (CR1) who underwent hematopoietic stem cell transplant (HCT) and were randomized to receive gilteritinib or placebo beginning after the time of engraftment for a two year period.
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 Aug 2017
Longer than P75 for phase_3
118 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 1, 2016
CompletedFirst Posted
Study publicly available on registry
December 19, 2016
CompletedStudy Start
First participant enrolled
August 16, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 7, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 9, 2023
CompletedResults Posted
Study results publicly available
September 19, 2024
CompletedJanuary 17, 2025
January 1, 2025
5.4 years
December 1, 2016
May 6, 2024
January 15, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Relapse-free Survival (RFS)
RFS was defined as the time from the date of randomization until the date of documented morphological relapse, or death from any cause, whichever occurred first. Morphological relapse was defined as documentation of any of the following events: * BM blasts ≥ 5% (not attributable to regenerating BM) * Any circulating blasts (not attributable to regenerating BM or growth factors) * Presence of extramedullary blast foci per Revised International Working Group (RIWG) criteria * The earliest date of any of the relapse event was used for RFS.
From the date of randomization up to 64 months and 22 days
Secondary Outcomes (11)
Overall Survival (OS)
From the date of randomization up to 64 months and 22 day
Number of Participants With Treatment Emergent Adverse Events (TEAE)
From the date of randomization through 30 days after the last dose, up to 25 months and 22 days
Karnofsky Performance Status Scores
Baseline, month 24
Percentage of Participants With Non-relapse Mortality (NRM)
From the date of randomization up to 64 months and 22 days
Event-free Survival (EFS)
From the date of randomization up to 64 months and 22 days
- +6 more secondary outcomes
Study Arms (2)
Gilteritinib
EXPERIMENTALParticipants received gilteritinib 120 milligrams (mg) (three tablets of 40 mg) orally, once daily (QD) for up to 2 years or until a protocol-defined discontinuation criterion was met.
Placebo
PLACEBO COMPARATORParticipants received gilteritinib matching placebo orally, QD for up to 2 years or until a protocol-defined discontinuation criterion was met.
Interventions
Eligibility Criteria
You may qualify if:
- Participant is considered a suitable candidate for HCT and has an acceptable source of allogeneic donor stem cells, as defined per institutional practice (allogeneic HCT for any donor source \[matched sibling, unrelated donor (URD), mismatched URD, related haploidentical, or umbilical cord blood\] and any graft source \[umbilical cord, BM, peripheral blood (PB)\], and any conditioning \[myeloablative conditioning (MAC), reduced intensity conditioning (RIC), or non-myeloablative conditioning (NMA)\] will be permitted).
- Participant is considered a legal adult by local regulation at the time of signing informed consent form (ICF).
- Participant consents to allow access to diagnostic BM aspirate or PB sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic that is being developed in parallel with gilteritinib.
- Participant has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as \< 5% blasts in the BM with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
- Participant has not received more than 2 cycles of induction chemotherapy to achieve CR1. The induction cycles can be the same regimen or different regimens. The regimen(s) may contain conventional agents, investigational agents, or a combination of both.
- Participants with CR with incomplete count recovery (CRp or CRi) are allowed. Incomplete platelet recovery (CRp) is defined as CR with platelet count \< 100 x 109/L. Incomplete blood count recovery (CRi) is defined as CR with residual neutropenia \< 1 x 109/L with or without complete platelet recovery. Red blood cell count (RBC) and platelet transfusion independence is not required.
- The maximum time allowed from establishment of CR1 to registration is 12 months.
- Participant has presence of the FLT3/ITD activating mutation in the BM or PB as determined by the local institution at diagnosis.
- Participant must meet the following criteria as indicated on the clinical laboratory tests:
- Serum creatinine within normal range, or if serum creatinine outside normal range, then glomerular filtration rate (GFR) \> 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault equation with adjustment if total body weight is ≥ 125% of ideal body weight.
- Total bilirubin (TBL) ≤ 2.5 mg/dL, except for participants with Gilbert's syndrome.
- Serum AST and/or alanine aminotransferase (ALT) \< 3 x institutional upper limit of normal (ULN).
- Participant has left ventricular ejection fraction at rest ≥ 40%.
- Participant has diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) ≥ 50% predicted and/or forced expiratory volume in 1 second (FEV1) ≥ 50% predicted.
- Female participants must either:
- +34 more criteria
You may not qualify if:
- Participant has had a prior allogeneic transplant.
- Participant has Karnofsky performance status score \< 70% .
- Participant requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of start of study drug.
- Participant requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the participant.
- Participant has a Fridericia-corrected QT interval (QTcF) \> 450 msec (average of triplicate determinations) per central read.
- Participant has long QT Syndrome at screening.
- Participant has a known infection with human immunodeficiency virus (HIV).
- Participant has active hepatitis B infection as determined by NAAT or surface antigen assay. Participants who have acquired immunity from past exposure (HBcAb positive / HBsAb positive / HBsAg negative) are eligible.
- Participant has active hepatitis C infection as determined by NAAT. NAAT must be performed if the participant has positive serology for hepatitis C. Participants who have had past exposure and have no detectable virus either through spontaneous clearance or treatment are eligible.
- Participant has an uncontrolled infection. If a bacterial or viral infection is present, the participant must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to registration. If a fungal infection is present, the participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to registration.
- Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection.
- Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Participant has had a myocardial infarction within 6 months prior to registration or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
- Participant has a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Participant is breast feeding or pregnant.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (118)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Mayo Clinic
Phoenix, Arizona, 85054, United States
Virginia G Piper Cancer Center
Scottsdale, Arizona, 85258, United States
University of California San Francisco
San Francisco, California, 94143, United States
Stanford University
Stanford, California, 94305, United States
Yale University School of Medicine
New Haven, Connecticut, 06511, United States
University of Florida
Gainesville, Florida, 32610, United States
University of Miami
Miami, Florida, 33136, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University
Atlanta, Georgia, 30322, United States
Northside
Atlanta, Georgia, 30342, United States
Augusta University
Augusta, Georgia, 30912, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Indiana Blood and Marrow Transplant
Indianapolis, Indiana, 46237, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160-7233, United States
University of Maryland Medical Systems
Baltimore, Maryland, 21201, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21231, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Massachusetts
Worcester, Massachusetts, 01655, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
University of Minnesota School of Medicine
Minneapolis, Minnesota, 55455, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University in St. Louis
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Memorial Sloan Kettering
New York, New York, 10065, United States
Weill Cornell Medical Center
New York, New York, 10065, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
University Hospitals of Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Ohio State University, The
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84143, United States
Intermountain BMT
Salt Lake City, Utah, 84143, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
West Virginia University Hospital
Morgantown, West Virginia, 26506-9214, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Site AU61001
Liverpool, Australia
Site AU61002
Melbourne, Australia
Site AU61004
Westmead, Australia
Site BE32003
Brussels, Belgium
Site BE32004
Ghent, Belgium
Site CA15004
Hamilton, Canada
Site CA15003
Montreal, Canada
Site DK45002
Aarhus, Denmark
Site DK45001
Copenhagen, Denmark
Site FR33007
Lille, France
Site FR33004
Lyon, France
Site FR33005
Paris, France
Site FR33008
Pessac, France
Site FR33010
Vandœuvre-lès-Nancy, France
Site DE49006
Cologne, Germany
Site DE49002
Düsseldorf, Germany
Site DE49003
Halle, Germany
Site DE49005
Hamburg, Germany
Site DE49007
Mainz, Germany
Site DE49004
Münster, Germany
Site GR30004
Athens, Greece
Site GR30003
Rio, Greece
Site GR30001
Thessaloniki, Greece
Site IT39005
Bergamo, Italy
Site IT39006
Bologna, Italy
Site IT39009
Genova, 16132, Italy
Site IT39002
Milan, Italy
Site IT39007
Milan, Italy
Site IT39011
Pescara, Italy
Site IT39003
Roma, Italy
Site IT39004
Udine, Italy
Site JP81014
Anjo, Aichi-ken, Japan
Site JP81011
Nagoya, Aichi-ken, Japan
Site JP81018
Sapporo, Hokkaido, Japan
Site JP81021
Kobe, Hyōgo, Japan
Site JP81012
Nishinomiya, Hyōgo, Japan
Site JP81002
Isehara, Kanagawa, Japan
Site JP81007
Yokohama, Kanagawa, Japan
Site JP81010
Sendai, Miyagi, Japan
Site JP81006
Suita, Osaka, Japan
Site JP81008
Shimotsuke, Tochigi, Japan
Site JP81013
Bunkyo-ku, Tokyo, Japan
Site JP81004
Chuo-ku, Tokyo, Japan
Site JP81016
Minato-ku, Tokyo, Japan
Site JP81020
Shinjuku-ku, Tokyo, Japan
Site JP81001
Fukuoka, Japan
Site JP81003
Fukuoka, Japan
Site JP81015
Kyoto, Japan
Site JP81017
Okayama, Japan
Site JP81005
Osaka, Japan
Site NZ64002
Christchurch, New Zealand
Site NZ64001
Grafton, 1010, New Zealand
Site PL48004
Warsaw, Poland
Site KR82001
Seoul, South Korea
Site KR82002
Seoul, South Korea
Site KR82003
Seoul, South Korea
Site KR82004
Seoul, South Korea
Site KR82005
Seoul, South Korea
Site ES34004
Barcelona, 08036, Spain
Site ES34005
Barcelona, Spain
Site ES34006
Salamanca, Spain
Site ES34007
Santander, Spain
Site ES34002
Valencia, Spain
Site TW88603
Taichung, Taiwan
Site TW88602
Taipei, Taiwan
Site TW88605
Taoyuan District, Taiwan
Site GB44010
Birmingham, United Kingdom
Site GB44003
Bristol, United Kingdom
Site GB44009
Glasgow, G12 0YN, United Kingdom
Site GB44004
London, United Kingdom
Site GB44002
Manchester, United Kingdom
Site GB44001
Sutton, United Kingdom
Related Publications (5)
Levis MJ, Hamadani M, Logan BR, Jones RJ, Singh AK, Litzow MR, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Oshima MU, Uy GL, Waller EK, Vasu S, Solh M, Mishra A, Muffly LS, Kim HJ, Stelljes M, Najima Y, Onozawa M, Thomson K, Chen C, Hasabou N, Rosales M, Hill JE, Gill SC, Nuthethi R, King D, Mendizabal A, Devine SM, Horowitz MM, Chen YB. Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia. Blood Adv. 2025 Oct 28;9(20):5123-5133. doi: 10.1182/bloodadvances.2025016306.
PMID: 40590852DERIVEDLevis MJ, Hamadani M, Logan BR, Jones RJ, Singh AK, Litzow MR, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Oshima MU, Uy GL, Waller EK, Vasu S, Solh M, Mishra A, Muffly LS, Kim HJ, Stelljes M, Najima Y, Onozawa M, Thomson K, Nagler A, Wei AH, Marcucci G, Chen C, Hasabou N, Rosales M, Hill J, Gill SC, Nuthethi R, King D, Mendizabal A, Devine SM, Horowitz MM, Chen YB. Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML. Blood. 2025 May 8;145(19):2138-2148. doi: 10.1182/blood.2024025154.
PMID: 39775763DERIVEDHamilton BK, Pandya BJ, Ivanescu C, Elsouda D, Hamadani M, Chen YB, Levis MJ, Ueda Oshima M, Litzow MR, Soiffer RJ, Ustun C, Perl AE, Singh AK, Geller N, Hasabou N, Rosales M, Cella D, Corredoira L, Pestana C, Horowitz MM, Logan B. Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+ acute myeloid leukemia. Blood Adv. 2024 Oct 8;8(19):5091-5099. doi: 10.1182/bloodadvances.2024013746.
PMID: 39167766DERIVEDPandya BJ, Burns LJ, Wang T, Xie B, Touya M, Spalding J, Block A, Kuperman G, Young C. Clinical Outcomes and Treatment Patterns in Adults With FLT3-ITDmut+ Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the United States and Canada. Transplant Cell Ther. 2024 Jul;30(7):683.e1-683.e13. doi: 10.1016/j.jtct.2024.04.016. Epub 2024 Apr 23.
PMID: 38663769DERIVEDLevis MJ, Hamadani M, Logan B, Jones RJ, Singh AK, Litzow M, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Ueda Oshima M, Uy GL, Waller EK, Vasu S, Solh M, Mishra A, Muffly L, Kim HJ, Mikesch JH, Najima Y, Onozawa M, Thomson K, Nagler A, Wei AH, Marcucci G, Geller NL, Hasabou N, Delgado D, Rosales M, Hill J, Gill SC, Nuthethi R, King D, Wittsack H, Mendizabal A, Devine SM, Horowitz MM, Chen YB; BMT-CTN 1506/MORPHO Study Investigators. Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3. J Clin Oncol. 2024 May 20;42(15):1766-1775. doi: 10.1200/JCO.23.02474. Epub 2024 Mar 12.
PMID: 38471061DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Transparency
- Organization
- Astellas Pharma Global Development, Inc
Study Officials
- STUDY DIRECTOR
Senior 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
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
December 1, 2016
First Posted
December 19, 2016
Study Start
August 16, 2017
Primary Completion
January 7, 2023
Study Completion
May 9, 2023
Last Updated
January 17, 2025
Results First Posted
September 19, 2024
Record last verified: 2025-01
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/.