The purpose of this study is to compare relapse-free survival (RFS) between subjects with
FMS-like tyrosine kinase 3 (FLT3) / internal tandem duplication (ITD) acute myeloid leukemia
(AML) in first complete remission (CR1) and who are randomized to receive gilteritinib or
placebo beginning after completion of induction/consolidation chemotherapy for a two-year
Subjects in CR1 will be approached for this study after induction/consolidation therapy is
complete and a decision not to proceed with transplantation is made or a suitable donor could
not be identified. Subjects will be randomized in a 2:1 ratio to receive gilteritinib or
placebo. Subjects will enter the screening period up to 14 days prior to the start of
treatment. Subjects will be administered treatment over continuous 28-day cycles. After
treatment discontinuation, subjects will have a 30-day follow-up visit for safety, after
which the subjects will enter the long-term follow up period for collection of subsequent AML
treatment, remission status, and survival (cause of death and date of death). Gilteritinib or
placebo will be given daily for up to 2 years. Subjects will be followed for up to 3 years
from the subjects 30-day follow up, or until 80% of the subjects have an RFS event, whichever
comes first. Study drug will not be provided during the follow-up period.
- Subject is considered an adult according to local regulation at the time of obtaining
consent form (ICF).
- Subject consents to allow access to subject's diagnostic bone marrow aspirate or
peripheral blood sample and/or the DNA derived from that sample, if available, that
may be used to validate a companion diagnostic test that is being developed in
parallel with gilteritinib.
- Subject has confirmed morphologically documented AML, excluding acute promyelocytic
leukemia (APL), in CR1 (including CRp and CRi). For the purposes of enrollment, CR
will be defined as < 5% blasts in the bone marrow with no morphologic characteristics
of acute leukemia (e.g., Auer rods) in the bone marrow with no evidence of
extramedullary disease such as central nervous system involvement or granulocytic
- Subject will not proceed with transplantation as either a decision not to proceed with
transplantation has been made either on the recommendation of the treating physician
or by the patient or a suitable donor could not be identified.
- Subject is < 2 months from the start of the last cycle of consolidation and should
have completed the recommended number of consolidations per local practice.
- Subject has had no use of investigational agents, with the exception of FLT3
inhibiting agents during induction and/or consolidation therapy, within the prior 4
- Subject has had presence of the FLT3/ITD activating mutation in the bone marrow or
peripheral blood as determined by the local institution at diagnosis.
- Subject has an ECOG performance status 0 to 2.
- Subject must meet the following criteria as indicated on the clinical laboratory
- Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN), or if serum
creatinine outside normal range, then glomerular filtration rate (GFR) > 40
mL/min/1.73m^2 as calculated with the 4-parameter Modification of Diet in Renal
Disease (MDRD) equation.
- Serum total bilirubin ≤ 2.5 mg/dL (43 μmol/L), except for subjects with Gilbert's
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x
- Serum potassium and serum magnesium ≥ institutional lower limit of normal (LLN).
- Absolute neutrophil count (ANC) ≥ 500/μl and platelets ≥ 20000/μl (unsupported by
- Subject is suitable for oral administration of study drug.
- Female subject must either:
- Be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses) prior to
- Documented surgically sterile or status posthysterectomy (at least 1 month prior
- Or, if of childbearing potential,
- Agree not to try to become pregnant during the study and for 6 months after the
final study drug administration
- And have a negative urine or 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.
- Female subject must agree not to breastfeed starting at screening and throughout the
study period, and for 2 months and 1 week after the final study drug administration.
- Female subject must not donate ova starting at screening and throughout the study
period, and for 6 months after the final study drug administration.
- Male subject and subject's female partners who are of childbearing potential must be
using highly effective contraception per locally accepted standards (in addition to a
barrier method) starting at screening and continue throughout the study period and for
4 months and 1 week after the final study drug administration.
- Male subject must not donate sperm starting at screening and throughout the study
period and for 4 months and 1 week after the final study drug administration.
- Subject agrees not to participate in another interventional study while on treatment.
- Subject has had prior allogeneic transplant.
- Subject has QTcF interval > 450 msec (average of triplicate determinations based on
- Subject with Long QT Syndrome.
- Subject with hypokalemia and hypomagnesemia at screening (defined as values below
- Subject has clinically active central nervous system leukemia.
- Subject is known to have human immunodeficiency virus infection.
- Subject has active hepatitis B or C.
- Subject has an uncontrolled infection. If a bacterial or viral infection is present,
the subject 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
subject must be receiving definitive systemic anti-fungal therapy and have no signs of
progressing infection for 1 week prior to randomization.
- Subject has progressing infection 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.
- Subject has uncontrolled angina, severe uncontrolled ventricular arrhythmias,
electrocardiographic evidence of acute ischemia, congestive heart failure New York
Heart Association (NYHA) class 3 or 4 or subject has a history of congestive heart
failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated
acquisition (MUGA) scan performed within 1 month prior to study entry results in a
left ventricular ejection fraction that is ≥ 45%.
- Subject requires treatment with concomitant drugs that are strong inducers of
cytochrome P450 (CYP) 3A.
- Subject requires treatment with concomitant drugs that are strong inhibitors or
inducers of P-glycoprotein (P-gp) with the exception of drugs that are considered
absolutely essential for the care of the subject.
- Subject requires treatment with concomitant drugs that target serotonin
5-hydroxytryptamine receptor 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 subject.
- Subject has a serious medical or psychiatric illness likely to interfere with
participation in this clinical study.
- Subject has prior malignancies, except resected basal cell carcinoma 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
- Subject has any condition which makes the subject unsuitable for study participation.