Subjects diagnosed with FLT3/ITD acute myeloid leukemia (AML) in CR1, including CRp and CRi, for whom a decision not to proceed with transplantation has been made, or a suitable donor could not be identified. MedDRA version: 19.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is considered an adult according to local regulation at the time of signing informed consent form (ICF). 3. Subject consents to allow access to his or her 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. 4. Subject has confirmed morphologically documented AML in CR1 (including CRp and CRi). For the purposes of enrollment, CR will be defined as 40 mL/min/1.73m2 as calculated with the 4-parameter Modification of Diet in Renal Disease (MDRD) equation. - Serum total bilirubin /= institutional lower limit of normal (LLN). - Absolute neutrophil count (ANC) >/= 500/µl and platelets >/= 20000/mcl (unsupported by transfusions). 11. Subject is suitable for oral administration of study drug. For Inclusion Criteria 12-17 see Protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. Subject has had prior allogeneic transplant. 2. Subject has QTcF interval > 450 msec (average of triplicate determinations). 3. Subject with Long QT Syndrome. 4. Subject with hypokalemia and hypomagnesemia at screening (defined as values below LLN). 5. Subject has clinically active central nervous system leukemia. 6. Subject is known to have human immunodeficiency virus infection. 7. Subject has active hepatitis B or C. 8. 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. 9. 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. 10. 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%. 11. Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A. 12. 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. 13. 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. For Exclusion Criteria 14-16 see Protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare relapse-free survival (RFS) between subjects with FLT3/ITD AML in first complete remission (CR1) without transplant and who are randomized to receive gilteritinib or placebo beginning after completion of induction/consolidation chemotherapy for a 2-year period.;Secondary Objective: Key Secondary Objective: - Compare overall survival (OS) in subjects treated with gilteritinib as maintenance therapy after induction/consolidation with those treated with placebo. Additional Secondary Objectives: - Event-free survival (EFS), AEs, clinical laboratory, vital signs, electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) performance scores. - Examine the relationship of minimal residual disease (MRD), as determined using a next-generation sequencing (NGS) platform specific to FLT3/ITD mutations, with RFS and OS.;Primary end point(s): Relapse-free survival (RFS) Leukemia relapse will be defined as bone marrow blasts 5% or higher (not attributable to regenerating bone marrow), any circulating blasts, any extramedullary blast foci as per Revised International Working Group (IWG) criteria.;Timepoint(s) of evaluation of this end point: RFS: the time from randomization until relapse or death from any cause, whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: - Overall survival (OS) Additional secondary efficacy endpoints: - Event-free survival (EFS) - Minimal residual disease (MRD) Safety Endpoints - AEs - Serum chemistry, hematology, coagulation and urinalysis - Vital signs - ECGs - Physical examination findings - Eastern Cooperative Oncology Group (ECOG) performance status;Timepoint(s) of evaluation of this end point: OS: the time from randomization until death from any cause. | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, Croatia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Democratic People's Republic of, Poland, Portugal, Romania, Serbia, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactService Desk - Global Clinical Dev.
Astellas Pharma Europe B.V.
Outcome results
None listed