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)
NCT ID: NCT02997202
Last Updated: 2025-01-17
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
356 participants
INTERVENTIONAL
2017-08-16
2023-05-09
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Gilteritinib
Participants 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.
gilteritinib
oral
Placebo
Participants received gilteritinib matching placebo orally, QD for up to 2 years or until a protocol-defined discontinuation criterion was met.
Placebo
oral
Interventions
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gilteritinib
oral
Placebo
oral
Eligibility Criteria
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Inclusion Criteria
* 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:
* Be of non-childbearing potential:
* postmenopausal (defined as at least 1 year without menses) prior to screening or
* documented as surgically sterilized (at least 1 month prior to the screening visit)
* Or, if of childbearing potential,
* Agree not to try to become pregnant during the study for 6 months after the final study drug administration
* And have a negative serum pregnancy test at screening
* And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after the final study drug administration.
* For United Kingdom sites:
* Highly effective forms of birth control include:
* Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
* Established intrauterine device (IUD) or intrauterine system (IUS)
* Female participants must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
* Male participants (even if surgically sterilized), and partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period and for 127 days after the final study drug administration.
* For United Kingdom sites:
* Highly effective forms of birth control include:
* Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
* Established IUD or IUS
* Vasectomy (A vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.)
* Male is sterile due to a bilateral orchiectomy
* Male participants must not donate sperm throughout the study drug treatment period and for 127 days after the final study drug administration.
* Participant is able to take an oral medication.
* Participant agrees not to participate in another interventional study while on treatment.
* Participant is ≥ 30 days and ≤ 90 days from hematopoietic cell infusion.
* Participant has achieved engraftment. Engraftment is defined as ANC ≥ 500 cells/μL and platelets ≥ 20000/μL on 3 consecutive measurements (each occurring at least 1 day apart). The participant must not have had a platelet transfusion within 7 days prior to the first measurement.
* Participant has confirmed ongoing morphologically documented AML in CR1. For the purposes of randomization, CR1 will be defined as \< 5% blasts 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 meets the following criteria as indicated on the clinical laboratory tests:
* Serum creatinine within normal range, or if serum creatinine outside normal range, then 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.
* TBL \< 2.5 mg/dL, except for participants with Gilbert's syndrome.
* Serum AST and/or ALT \< 3 x institutional ULN.
* Serum potassium and magnesium ≥ the institutional lower limit of normal (LLN).
* If the participant has developed overall grades II-IV acute GVHD, the following criteria must be met to be randomized:
* No requirement of \> 0.5 mg/kg of prednisone (or equivalent) daily dose within 1 week of randomization
* No escalation of systemic immunosuppression in terms of increase of corticosteroids or addition of new agent / modality within 2 weeks of randomization. (Note that increasing calcineurin inhibitors or sirolimus to achieve therapeutic trough levels is allowed.) Topical skin and topical gastrointestinal steroids are allowed.
* Participant is able to take oral medication.
Exclusion Criteria
* 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.
* Participant has prior malignancies, except lobular breast carcinoma in situ, fully resected basal cell or squamous cell carcinoma of skin or treated cervical carcinoma in situ.
Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously will not be allowed.
* Participant requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of starting study drug.
* Participant requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered by the investigator to be absolutely essential for the care of the participant and for which no acceptable alternative exists.
* Participant has a QTcF interval \> 450 msec (average of triplicate determinations) by central read.
* Participant has a need for supplemental oxygen with the exception of using previously existing non-invasive continuous positive airway pressure (CPAP) at night.
* Participant has used investigational agents within 4 weeks of randomization.
* Participant has used experimental therapy for acute GVHD within 4 weeks of randomization. If unsure of the definition of "experimental", discussion with one of the protocol chairs is recommended.
* 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 randomization. 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 randomization.
* 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.
18 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
Blood and Marrow Transplant Clinical Trials Network
NETWORK
Astellas Pharma Global Development, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Senior Medical Director
Role: STUDY_DIRECTOR
Astellas Pharma Global Development, Inc.
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic
Phoenix, Arizona, United States
Virginia G Piper Cancer Center
Scottsdale, Arizona, United States
University of California San Francisco
San Francisco, California, United States
Stanford University
Stanford, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
University of Florida
Gainesville, Florida, United States
University of Miami
Miami, Florida, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, United States
Emory University
Atlanta, Georgia, United States
Northside
Atlanta, Georgia, United States
Augusta University
Augusta, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Indiana Blood and Marrow Transplant
Indianapolis, Indiana, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
University of Maryland Medical Systems
Baltimore, Maryland, United States
Johns Hopkins Hospital
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Massachusetts
Worcester, Massachusetts, United States
Karmanos Cancer Center
Detroit, Michigan, United States
University of Minnesota School of Medicine
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University in St. Louis
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Memorial Sloan Kettering
New York, New York, United States
Weill Cornell Medical Center
New York, New York, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
University Hospitals of Cleveland Medical Center
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Ohio State University, The
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Intermountain BMT
Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
West Virginia University Hospital
Morgantown, West Virginia, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 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, , 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, , 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, , 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, , United Kingdom
Site GB44004
London, , United Kingdom
Site GB44002
Manchester, , United Kingdom
Site GB44001
Sutton, , United Kingdom
Countries
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References
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Levis MJ, Hamadani M, Logan BR, Jones RJ, Singh AK, Litzow MR, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Ueda Oshima M, Uy GL, Waller EK, Vasu S, Solh MM, Mishra A, Muffly LS, Kim HJ, Stelljes M, Najima Y, Onozawa M, Thomson KJ, Chen C, Hasabou N, Rosales M, Hill JE, Gill SC, Nuthethi R, King D, Mendizabal AM, 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 Jul 1:bloodadvances.2025016306. doi: 10.1182/bloodadvances.2025016306. Online ahead of print.
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, 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.
Hamilton 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.
Pandya 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.
Levis 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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Link to plain language summary of the study on the Trial Results Summaries website
Other Identifiers
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2016-001061-83
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
BMT CTN 1506
Identifier Type: OTHER
Identifier Source: secondary_id
2215-CL-0304
Identifier Type: -
Identifier Source: org_study_id
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