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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Placebo; Drug: gilteritinib

Detailed Description

Participants with FLT3/ITD AML in first morphologic complete remission (CR1) undergone allogeneic hematopoietic stem cell transplant (HCT) were randomized to receive gilteritinib or placebo 30 to 90 days after HCT for a two year period. Participants wiere stratified according to: 1) conditioning regimen intensity (myeloablative vs. reduced intensity/non-myeloablative), 2) time from first day of hematopoietic cell infusion to randomization (30-60 days vs. 61-90 days) and 3) presence vs absence of or unknown minimal residual disease (MRD) from the most recent pre-registration bone marrow (BM) aspirate.

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 3

Expanded Access

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Contacts and Locations

Study Locations

• Australia
  • Liverpool, Australia
    • Site AU61001
  • Melbourne, Australia
    • Site AU61002
  • Westmead, Australia
    • Site AU61004
• Belgium
  • Bruxelles, Belgium
    • Site BE32003
  • Gent, Belgium
    • Site BE32004
• Canada
  • Hamilton, Canada
    • Site CA15004
  • Montreal, Canada
    • Site CA15003
• Denmark
  • Arhus, Denmark
    • Site DK45002
  • Copenhagen, Denmark
    • Site DK45001
• France
  • Lille, France
    • Site FR33007
  • Lyon, France
    • Site FR33004
  • Paris, France
    • Site FR33005
  • Pessac, France
    • Site FR33008
  • Vandoeuvre-Les-Nancy, France
    • Site FR33010
• Germany
  • Düsseldorf, Germany
    • Site DE49002
  • Halle (Saale), Germany
    • Site DE49003
  • Hamburg, Germany
    • Site DE49005
  • Köln, Germany
    • Site DE49006
  • Mainz, Germany
    • Site DE49007
  • Münster, Germany
    • Site DE49004
• Greece
  • Athens, Greece
    • Site GR30004
  • Rio, Greece
    • Site GR30003
  • Thessaloniki, Greece
    • Site GR30001
• Italy
  • Bergamo, Italy
    • Site IT39005
  • Bologna, Italy
    • Site IT39006
  • Genova, Italy, 16132
    • Site IT39009
  • Milano, Italy
    • Site IT39002
  • Milano, Italy
    • Site IT39007
  • Pescara, Italy
    • Site IT39011
  • Roma, Italy
    • Site IT39003
  • Udine, Italy
    • Site IT39004
• Japan
  • Fukuoka, Japan
    • Site JP81003
  • Fukuoka, Japan
    • Site JP81001
  • Kyoto, Japan
    • Site JP81015
  • Okayama, Japan
    • Site JP81017
  • Osaka, Japan
    • Site JP81005
  • Aichi
    • Anjo, Aichi, Japan
      • Site JP81014
    • Nagoya, Aichi, Japan
      • Site JP81011
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Site JP81018
  • Hyogo
    • Kobe, Hyogo, Japan
      • Site JP81021
    • Nishinomiya, Hyogo, Japan
      • Site JP81012
  • Kanagawa
    • Isehara, Kanagawa, Japan
      • Site JP81002
    • Yokohama, Kanagawa, Japan
      • Site JP81007
  • Miyagi
    • Sendai, Miyagi, Japan
      • Site JP81010
  • Osaka
    • Suita, Osaka, Japan
      • Site JP81006
  • Tochigi
    • Shimotsuke, Tochigi, Japan
      • Site JP81008
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Site JP81013
    • Chuo-ku, Tokyo, Japan
      • Site JP81004
    • Minato-ku, Tokyo, Japan
      • Site JP81016
    • Shinjuku-ku, Tokyo, Japan
      • Site JP81020
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Site KR82001
  • Seoul, Korea, Republic of
    • Site KR82005
  • Seoul, Korea, Republic of
    • Site KR82002
  • Seoul, Korea, Republic of
    • Site KR82004
  • Seoul, Korea, Republic of
    • Site KR82003
• New Zealand
  • Christchurch, New Zealand
    • Site NZ64002
  • Grafton, New Zealand, 1010
    • Site NZ64001
• Poland
  • Warszawa, Poland
    • Site PL48004
• Spain
  • Barcelona, Spain
    • Site ES34005
  • Barcelona, Spain, 08036
    • Site ES34004
  • Salamanca, Spain
    • Site ES34006
  • Santander, Spain
    • Site ES34007
  • Valencia, Spain
    • Site ES34002
• Taiwan
  • Taichung, Taiwan
    • Site TW88603
  • Taipei, Taiwan
    • Site TW88602
  • Taoyuan, Taiwan
    • Site TW88605
• United Kingdom
  • Birmingham, United Kingdom
    • Site GB44010
  • Bristol, United Kingdom
    • Site GB44003
  • Glasgow, United Kingdom, G12 0YN
    • Site GB44009
  • London, United Kingdom
    • Site GB44004
  • Manchester, United Kingdom
    • Site GB44002
  • Sutton, United Kingdom
    • Site GB44001
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
    • Scottsdale, Arizona, United States, 85258
      • Virginia G Piper Cancer Center
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30342
      • Northside
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplant
  • Kansas
    • Kansas City, Kansas, United States, 66160-7233
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Systems
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota School of Medicine
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University, The
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Intermountain BMT
    • Salt Lake City, Utah, United States, 84143
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9214
      • West Virginia University Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Registration Inclusion Criteria

• 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:

  • 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.

Randomization Inclusion Criteria

• 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.

Registration Exclusion Criteria

• 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.
• 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.

Randomization Exclusion Criteria

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: gilteritinib; oral
Placebo Comparator: Placebo; Participants received gilteritinib matching placebo orally, QD for up to 2 years or until a protocol-defined discontinuation criterion was met.	Drug: Placebo; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization until the date of death from any cause (death date - first dose date + 1). For a Participant who were 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 - first dose date + 1).	From the date of randomization up to 64 months and 22 day
Number of Participants With Treatment Emergent Adverse Events (TEAE)	An Adverse event (AE) was any untoward medical occurrence in a participant administered a study drug, and which did not have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether considered related to the medicinal product. TEAE defined as an AE event observed through 30 days after the last dose.	From the date of randomization through 30 days after the last dose, up to 25 months and 22 days
Karnofsky Performance Status Scores	KPS scores of participants were reported. KPS was a standard way of measuring ability of cancer participants to perform ordinary tasks. It was 11 level score which ranged between 0-100%. 100 =Normal, no complaints, no evidence of disease 90 =Able to carry on normal activity, minor signs or symptoms of disease 80 =Normal activity with effort, some signs or symptoms of disease 70 =Care for self, unable to carry on normal activity or to do work 60 =Required occasional assistance but was able to care for most of his needs 50 =Required considerable assistance & frequent medical care 40 =Disabled, required special care & assistance 30 = Severely disabled, hospitalization indicated, although death not imminent 20 =Very sick, hospitalization necessary, active supportive treatment necessary 10 =moribund fatal processes progressing rapidly 0 =Dead.	Baseline, month 24
Percentage of Participants With Non-relapse Mortality (NRM)	NRM was defined as death from any cause other than relapse or disease progression (DP). 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 RIWG criteria; The earliest date of any of the relapse event were used for RFS. DP: >=20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion. Incidence of NRM was estimated using the cumulative incidence function, treating relapse/progression as a competing risk.	From the date of randomization up to 64 months and 22 days
Event-free Survival (EFS)	EFS: Time from date of randomization until documented relapse, or premature discontinuation of treatment or initiation of other anti-leukemic treatment or death from any cause, whichever occurred first. Relapse was defined as documentation of any of 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 RIWG criteria; The earliest date of any of relapse event were used for RFS. Anti-leukemic treatment was defined as hypomethylating agents, chemotherapy, oral anticancer agents, Donor lymphocyte infusion (DLI) or cellular therapies given because of detectable disease, not meeting R-IWG criteria for relapse.	From the date of randomization up to 64 months and 22 days
Percentage of Participants With Treatment Emergent Acute Graft vs. Host Disease (aGVHD)	The cumulative incidence at 6 months after randomization of grades II-IV and grades III-IV aGVHD were reported, treating death prior to aGVHD as the competing risk. It was graded according to diagnosis and severity scoring used by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The acute GVHD algorithm calculated the grade based on the organ (skin, gastrointestinal (GI)and liver) stage and etiology/biopsy reported on the weekly GVHD form. Grade I aGVHD was defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II aGVHD was stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-4 for GI, or stage 2-3 of liver. Grade IV was stage 4 of skin, or stage 4 of liver. Grade IV was the worst outcome. Treatment emergent was defined as an event observed through 30 days after the last dose.	From the date of randomization up to 6 months
Percentage of Participants With Treatment Emergent Chronic GVHD at 12 Months	Chronic GVHD was graded according to diagnosis and severity scoring from the National Institute of Health (NIH) 2014 Consensus Criteria. Eight organs - skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia were scored on a 0-3 scale to reflect degree of chronic GVHD involvement, where 0 = no involvement/no symptoms & 3 indicated the worst symptom. This system staged severity in each individual organ, and then a global score defined as mild, moderate or severe, based on number of organs involved and organ severity score was calculated. The cumulative incidence of chronic GVHD (mild, moderate, severe) at 12 months after randomization was reported, treating death prior to chronic GVHD as the competing risk. Treatment emergent was defined as an event observed through 30 days after the last dose.	From the date of randomization up to 12 months
Percentage of Participants With Treatment Emergent Chronic GVHD at 24 Months	Chronic GVHD was graded according to diagnosis and severity scoring from the NIH 2014 Consensus Criteria. Eight organs- skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are scored on a 0-3 scale to reflect degree of chronic GVHD involvement where 0 = no involvement/no symptoms & 3 indicated the worst symptom. This system staged severity in each individual organ, and then a global score defined as mild, moderate or severe, based on number of organs involved and organ severity score was calculated. The cumulative incidence of chronic GVHD (mild, moderate, severe) at 24 months after randomization was reported, treating death prior to chronic GVHD as the competing risk. Treatment emergent was defined as an event observed through 30 days after the last dose.	From the date of randomization up to 24 months
Percentage of Participants With FMS-like Tyrosine Kinase 3/Internal Tandem Duplication (FLT3/ITD) Minimal Residual Disease (MRD)	The presence of MRD was considered Detectable in participants who were FLT3/ITD MRD undetectable prior to randomization if log10-transformed overall FLT3/ITD mutation ratio greater than -4 otherwise presence of MRD was considered Not Detectable. Participants who had detectable FLT3/ITD MRD prior to randomization were considered eradicated if log10-transformed overall FLT3/ITD mutation ratio ≤ -4. Incidence of MRD Eradication and Detection were estimated using the cumulative incidence function, treating death during MRD assessment period without documentation of MRD event as competing risk.	From the date of randomization up to 64 months and 22 days
Percentage of Participants With Relapse	Cumulative incidence of relapse was reported, treating death in remission as a competing risk. 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 RIWG criteria; The earliest date of any of the relapse event were used for RFS.	From the date of randomization up to 64 months and 22 days
Percentage of Participants With Treatment Emergent Infection by Severity.	Severity of Infection was assessed based on the following criteria: Grade 1-Mild Asymptomatic or mild symptoms, clinical or diagnostic observations noted intervention not indicated. Grade 2-Moderate Local or noninvasive intervention indicated. Grade 3-Severe Medically significant but not immediately life threatening, hospitalization or prolonged hospitalization. Grade 4-Life Threatening Life threatening consequences, urgent intervention indicated. Grade 5-Death related to the AE. Cumulative incidence of grade 3 to 5 infections were reported, treating death (grade 5) as a competing event. Treatment emergent was defined as an event observed through 30 days after the last dose.	From the date of randomization through 30 days after the last dose, up to 25 months and 22 days

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Blood and Marrow Transplant Clinical Trials Network
• Investigators: Study Director: Senior Medical Director, Astellas Pharma Global Development, Inc.

Publications and helpful links

Helpful Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): January 7, 2023
• Study Completion (Actual): May 9, 2023

Study Registration Dates

• First Submitted: December 1, 2016
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (Estimated): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 15, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Safety and Efficacy; ASP2215; Gilteritinib
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Gilteritinib
• Other Study ID Numbers: 2215-CL-0304; 2016-001061-83 (EudraCT Number); BMT CTN 1506 (Other Identifier: Blood and Marrow Transplant Clinical Trials Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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/.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No