A Study of ASP2215 (Gilteritinib), Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 (FLT3/ITD) Acute Myeloid Leukemia (AML) in First Complete Remission
Condition: Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) / Internal Tandem Duplication (ITD) Mutation
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Gilteritinib; Placebo
Intervention description: Oral tablet; Oral tablet
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 98.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute myeloid leukemia; First Complete Remission; gilteritinib; FLT3/ITD; AML; ASP2215

Summary:

      The purpose of this study was to compare relapse-free survival (RFS) between participants
      with FMS-like tyrosine kinase 3 (FLT3) / internal tandem duplication (ITD) acute myeloid
      leukemia (AML) in first complete remission (CR1) and who were randomized to receive
      gilteritinib or placebo beginning after completion of induction/consolidation chemotherapy
      for a two-year period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 for 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
             sarcoma.

          -  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
             weeks.

          -  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
             tests:

               -  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
                  syndrome.

               -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x
                  ULN.

               -  Serum potassium and serum magnesium ≥ institutional lower limit of normal (LLN).

               -  Absolute neutrophil count (ANC) ≥ 500/μl and platelets ≥ 20000/μl (unsupported by
                  transfusions).

          -  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
                  screening, or

               -  Documented surgically sterile or status posthysterectomy (at least 1 month prior
                  to screening)

               -  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.

        Exclusion Criteria:

          -  Subject has had prior allogeneic transplant.

          -  Subject has QTcF interval > 450 msec (average of triplicate determinations based on
             central reading).

          -  Subject with Long QT Syndrome.

          -  Subject with hypokalemia and hypomagnesemia at screening (defined as values below
             LLN).

          -  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
             allowed.

          -  Subject has any condition which makes the subject unsuitable for study participation.