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    The EU Clinical Trials Register currently displays   36399   clinical trials with a EudraCT protocol, of which   5997   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2016-001061-83
    Sponsor's Protocol Code Number:2215-CL-0304
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-03-24
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedDenmark - DHMA
    A.2EudraCT number2016-001061-83
    A.3Full title of the trial
    A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Trial of the FLT3 Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients with FLT3/ITD AML
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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.
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code number2215-CL-0304
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstellas Pharma Global Development, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstellas Pharma Global Development, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe B.V.
    B.5.2Functional name of contact pointService Desk - Global Clinical Dev.
    B.5.3 Address:
    B.5.3.1Street AddressSylviusweg 62
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 BE
    B.5.4Telephone number+31715455878
    B.5.5Fax number+31715455224
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namegilteritinib
    D.3.2Product code ASP2215
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNgilteritinib
    D.3.9.1CAS number ASP2215
    D.3.9.4EV Substance CodeSUB177203
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    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)
    E.1.1.1Medical condition in easily understood language
    AML is cancer of myeloid line of blood cells characterized by rapid growth of abnormal white blood cells that accumulate in bone marrow and interfere with production of normal blood cells
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10000886
    E.1.2Term Acute myeloid leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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
    E.2.2Secondary objectives of the trial
    1.To determine the safety and tolerability of gilteritinib after HCT.
    2.To compare overall survival (OS), non-relapse mortality (NRM) and event-free survival (EFS) (where events include relapse, death, stopping therapy and administration of donor lymphocyte infusion (DLI) or new therapy for suspicion of disease) in participants treated with gilteritinib as maintenance therapy after HCT compared to those treated with placebo.
    3.To compare 6-month cumulative incidence of grades II-IV and III-IV acute graft-versus host disease (GVHD) and 12-month and 24-month
    cumulative incidence of mild, moderate, and severe chronic GVHD in participants treated with gilteritinib as maintenance therapy after HCT
    compared to those treated with placebo.
    4.To examine the effect of pre- and post-transplant MRD on RFS and OS.
    5.To compare incidence and severity with gilteritinib as of infection in participants treated maintenance therapy after HCT compared to those
    treated with placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Subject is suitable candidate for HCT and has an acceptable source of allogeneic donor 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 blood count recovery (CRi) is defined as CR with residual neutropenia < 1 x 109/L with or without
    complete platelet recovery. Red blood cell count (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).
    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) ≥ 50%
    predicted and/or forced expiratory volume in 1 second (FEV1), ≥ 50% predicted.

    For all Registration Inclusion Criteria, see protocol.
    For a list of Randomization Eligibility Criteria and Randomization Inclusion Criteria, see protocol.
    E.4Principal 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 CYP3A (APPENDIX H) within 14 days of start of study drug.
    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) 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
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is RFS, treated as a time to event outcome. The primary analysis will be performed using the intent-to-treat principle so that all randomized participants will be included in the analysis. Leukemia relapse or death will be considered failures for this endpoint, which will be adjudicated by a blinded endpoint review committee.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The time from randomization to either leukemia relapse or death, whichever comes first.
    E.5.2Secondary 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
    E.5.2.1Timepoint(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
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA51
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Korea, Republic of
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of trial is defined as last-patient-last-contact
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 850
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 150
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 380
    F.4.2.2In the whole clinical trial 1000
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    All participants may remain on treatment for up to 2 years after randomization. After treatment discontinuation, long-term follow up for relapse and/or death will occur until 5 years after the last participant is randomized or until 80% of the relapse events have occurred, whichever comes first.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Froedtert and the Medical College of Wisconsin Clinical Cancer Center CIBMTR® | Milwaukee Campus
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-04-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-05-02
    P. End of Trial
    P.End of Trial StatusOngoing
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