FMS-like tyrosine kinase 3 (FLT3) / internal tandem duplication (ITD) (FLT3/ITD) acute myeloid leukemia (AML) in first morphologic complete remission (CR1) that has been treated with allogeneic hematopoietic stem cell transplant (HCT) MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: gilteritinib
Product Code: ASP2215
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: gilteritinib
CAS Number: ASP2215
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Astellas Pharma Global Development, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Subject is suitable candidate for HCT and has an acceptable source of 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). 2.IRB/IEC approved written ICF and privacy language obtained from the participant or legally authorized representative prior to any study-related procedures 3.Subject is legal adult by local regulation at the time of signing ICF 4.Subject consents to allow access to his or her diagnostic BM aspirate or PB sample and/or the DNA derived from that sample, if available. 5.Subject has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault equation with adjustment if total body weight is = 125% of ideal body weight. b.Total bilirubin (TBL) = 2.5 mg/dL, except for participants with Gilbert’s syndrome. c.Serum AST and/or alanine aminotransferase (ALT) =65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1.Participant has had a prior allogeneic transplant. 2.Participant has Karnofsky performance status score 450 msec (average of triplicate determinations) per central read. 6.Participant has long QT Syndrome at screening. 7.Participant has a known infection with human immunodeficiency virus (HIV) 8.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. 9.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. 10.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. 11.Participant has had a myocardial infarction within 6 months prior to registration or New York Heart Association (NYHA) Class III or IV heart failure (APPENDIX D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia. For all Registration Exclusion Criteria, see protocol. For a list of Randomization Exclusion Criteria, see protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare relapse-free survival (RFS) between participants with FLT3/ITD AML in CR1 who undergo HCT and are randomized to receive gilteritinib or placebo beginning after the time of engraftment for a two year period;Secondary Objective: The key secondary objective is to compare overall survival (OS) in participants treated with gilteritinib as maintenance therapy after HCT compared to those treated with placebo. ;Primary end point(s): The primary endpoint of this study is RFS. RFS will be measured from time of randomization to either morphological relapse or death, whichever comes first. ;Timepoint(s) of evaluation of this end point: The time from randomization to either morphological relapse or death, whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability Overall survival (OS) Non-relapse mortality Event-free survival (EFS) Cumulative incidence of acute graft-versus-host disease (GVHD) Cumulative incidence of chronic GVHD detection of minimal residual disease (MRD) Incidence and Severity of Infection;Timepoint(s) of evaluation of this end point: Safety and tolerability - measured from randomization through 30 days after end of study drug. OS - measured from randomization to date of death from any cause. Non-relapse mortality - measured from randomization through death. EFS - measured at 12 and 24 months after randomization. Cumulative incidence of acute GVHD - measured from randomization through 6 months after randomization Cumulative incidence of chronic GVHD - measured from randomization through 12 and 24 months after randomization. Detection of MRD - measured from pre-HCT through 24 months after randomization. Infection Assessment - measured from randomization through 12 and 24 months after randomization | — |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Greece, Italy, Japan, Korea, Republic of, New Zealand, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactService Desk - Global Clinical Dev.
Astellas Pharma Europe B.V.
Outcome results
None listed