This multi center Phase III clinical trial will evaluate impact of maintenance therapy (maintain the response achieved during the first course of treatment) with the FLT3 (FMS-like tyrosine kinase 3) inhibitor gilteritinib on the RFS (Relapse free survival) of participants with FLT3/ITD AML (FMS-like tyrosine kinase 3 / Internal tandem duplication Acute myeloid leukemia) who have successfully undergone allogeneic transplant.

Phase 1

Conditions: 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: 19.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-001061-83-ES

Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 1000

Inclusion Criteria

1.Subject is 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).
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 < 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.
a.Subject has not received more than 2 cycles of induction chemotherapy to achieve CR1.
b.Subjects 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 hematologic recovery (CRi) is defined as CR with residual neutropenia < 1 x 109/L with or without complete platelet recovery. RBC and platelet transfusion independence is not required.
c.The maximum time allowed from establishment of CR1 to registration is 12 months.
6.Subject has presence of the FLT3/ITD activating mutation in the BM or PB as determined by the local institution at diagnosis.
7.Subject must meet the following criteria as indicated on the clinical laboratory tests:
a.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.
b.Total bilirubin (TBL) = 2.5 mg/dL, except for participants with Gilbert’s syndrome.
c.Serum AST and/or alanine aminotransferase (ALT) < 3 x institutional upper limit of normal (ULN).
d.Serum potassium and magnesium greater than the institutional lower limit of normal (LLN).
8.Subject has left ventricular ejection fraction at rest = 40%.
9.Subject has diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) > 50% predicted.

For all Registration Inclusion Criteria, see protocol.
For a list of Randomization Eligibility Criteria and Randomization Inclusion Criteria, 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 850
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1.Participant has had a prior allogeneic transplant.
2.Participant has Karnofsky performance status score < 70% (APPENDIX F).
3.Participant requires treatment with concomitant drugs that are strong inducers of CYP3A4.
4.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.
5.Participant has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of triplicate determinations).
6.Participant has long QT Syndrome at screening.
7.Participant has a known infection with human immunodeficiency virus (HIV) as determined by serology or nucleic acid amplification test (NAAT).
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. Participants who have had past exposure and have no detectable virus either through spontaneous clearance or treatment are eligible.
10.Participant with uncontrolled infections will be excluded. 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.