Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38497   clinical trials with a EudraCT protocol, of which   6324   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-004890-28
    Sponsor's Protocol Code Number:AC220-007
    National Competent Authority:Czech Republic - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-12-23
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedCzech Republic - SUKL
    A.2EudraCT number2013-004890-28
    A.3Full title of the trial
    A Phase 3 Open-Label Randomized Study of Quizartinib (AC220) Monotherapy Versus Salvage Chemotherapy in Subjects with FLT3-ITD Positive Acute Myeloid Leukemia (AML) Refractory To or Relapsed After First-line Treatment With or Without Hematopoietic Stem Cell Transplant (HSCT) Consolidation.
    Otevřené randomizované klinické hodnocení fáze 3 přípravku Quizartinib (AC220) v monoterapii v porovnání se záchrannou chemoterapií u pacienttů s FLT3-ITD pozitivní akutní myeloidní leukémií (AML) refrakterní či relabující po první linii léčby s nebo bez konsolidační transplantace hematopoetických kmenových buněk (HSCT)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Open-Label clinical trial of the drug Quizartinib (AC220) compared to recovery treatment in patients with Acute Myeloid Leukemia (AML), a cancer of the blood.
    Otevřené klinické hodnocení fáze 3 přípravku quizartinib (AC220) v porovnání se standartní léčbou u pacientů s akutní myeloidní leukémií (AML), rakovinou krve.
    A.4.1Sponsor's protocol code numberAC220-007
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02039726
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1151-8078
    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 SponsorDaiichi Sankyo 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 supportDaiichi Sankyo Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo Inc
    B.5.2Functional name of contact pointClinical Trial Information Contact
    B.5.3 Address:
    B.5.3.1Street Address399 Thornall Street
    B.5.3.2Town/ cityEdison
    B.5.3.3Post codeNJ 08837
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 7325905000
    B.5.5Fax number+1 732 9065690
    B.5.6E-maileu_cta@dsi.com
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/09/622
    D.3 Description of the IMP
    D.3.1Product nameQuizartinib
    D.3.2Product code AC220
    D.3.4Pharmaceutical form 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 INNQuizartinib
    D.3.9.1CAS number 1132827-21-4
    D.3.9.2Current sponsor codeAC220
    D.3.9.3Other descriptive nameQUIZARTINIB
    D.3.9.4EV Substance CodeSUB89721
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 2
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/09/622
    D.3 Description of the IMP
    D.3.1Product nameQuizartinib
    D.3.2Product code AC220
    D.3.4Pharmaceutical form 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 INNQuizartinib
    D.3.9.1CAS number 1132827-21-4
    D.3.9.2Current sponsor codeAC220
    D.3.9.3Other descriptive nameQUIZARTINIB
    D.3.9.4EV Substance CodeSUB89721
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationCzech Republic
    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 nameCytarabine
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCytarabine
    D.3.9.1CAS number 147-94-4
    D.3.9.3Other descriptive nameCYTARABINE
    D.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationCzech Republic
    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 nameFludarabine
    D.3.4Pharmaceutical form Powder for solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFLUDARABINE
    D.3.9.1CAS number 21679-14-1
    D.3.9.4EV Substance CodeSUB07678MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationCzech Republic
    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 nameIdarubicin
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIdarubicin
    D.3.9.3Other descriptive nameIDARUBICIN
    D.3.9.4EV Substance CodeSUB08111MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationCzech Republic
    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.3.2Product code G-CSF
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFilgrastim
    D.3.9.1CAS number 143011-72-7
    D.3.9.3Other descriptive nameGRANULOCYTE COLONY-STIMULATING FACTOR
    D.3.9.4EV Substance CodeSUB14018MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg/m2 microgram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 7
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationCzech Republic
    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 nameCytarabine
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCytarabine
    D.3.9.1CAS number 147-94-4
    D.3.9.3Other descriptive nameCYTARABINE
    D.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Refractory or Relapsed FLT3-ITD Positive Acute Myeloid Leukemia (AML)
    Refrakterní či relabující FLT3-ITD pozitivní akutní myeloidní leukémie (AML)
    E.1.1.1Medical condition in easily understood language
    Acute Myeloid Leukemia (AML) a cancer of the blood.
    Akutní myeloidní leukémie (AML) rakovina krve
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to determine whether quizartinib monotherapy prolongs overall survival (OS) compared to salvage chemotherapy in subjects with FLT3-ITD positive AML who are refractory to or have relapsed within 6 months, after first-line AML therapy.
    Primárním cílem klinického hodnocení je zjistit, zda monoterapie quizartinibem prodlužuje celkové přežívání (OS) ve srovnání se záchrannou chemoterapií u subjektů s FLT3-ITD pozitivní AML refrakterních nebo relabujících do 6 měsíců od prvni linie terapie AML.
    E.2.2Secondary objectives of the trial
    The secondary objective is to determine event-free survival (EFS) with quizartinib versus salvage chemotherapy.
    Sekundárním cílem je stanovit dobu přežití bez selhání (EFS) u quizartinibu ve srovnání se záchrannou chemoterapií.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria
    To be able to participate in this study, candidates must meet the following criteria at screening
    or other specified time point:
    1. Provision of written informed consent approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) with privacy language in accordance with national regulations (eg, HIPAA authorization for US sites) prior to any study-related procedures, including withdrawal of prohibited medications if applicable.
    2. Age ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
    3. Morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS), as defined by World Health Organization criteria, as determined by pathology review at the study site.
    4. In first relapse (with duration of remission of 6 months or less) or refractory after prior therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone containing induction block at a standard dose.
    • Refractory is defined as:
    - After 1 cycle, a reduction in bone marrow blasts of less than 50% and failure to achieve a CR, CRp, or CRi.
    - After 2 cycles, lack of achievement of CR, CRp, or CRi
    • First relapse (with duration of remission of 6 months or less) is defined as:
    - Achievement of CR, CRi, or CRp, as defined by 2003 International Working
    Group criteria after initial AML therapy with or without consolidation or
    maintenance, and with or without HSCT.
    - Duration of CR, CRi or CRp is measured from the date of the bone marrow
    assessment which confirmed response or the date of allogeneic transplantation to the date of the bone marrow assessment that identified relapse or the appearance of peripheral blasts.
    5. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood (allelic ratio as determined by a central laboratory with a cutoff of ≥3% FLT3-ITD/total FLT3). If a specimen has been sent for FLT3-ITD testing at the central laboratory but the subject requires treatment for AML before the central FLT3-ITD test result is available, a local test result may be acceptable for randomization after consultation with the Medical Monitor.
    6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator’s assessment.
    7. ECOG performance score 0-2.
    8. Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for cytotoxic agents, or for at least 5 half-lives for non-cytotoxic agents.
    9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25 mL/min, as calculated with the Cockcroft-Gault formula.
    10. Serum potassium, magnesium, and calcium (serum calcium corrected for
    hypoalbuminemia) within institutional normal limits. Subjects with electrolytes outside the normal range will be eligible if these values are corrected upon retesting following any necessary supplementation.
    11. Total serum bilirubin ≤1.5×ULN.
    12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.
    Zařazovací kritéria
    Účast na tomto klinickém hodnocení vyžaduje splnění následujících kritérií při screeningu nebo v jiném určeném časovém bodu:
    1.Poskytnutí písemného informovaného souhlasu schváleného Etickou komisí s ochranou osobních údajů v souladu s vnitrostátními předpisy před veškerými postupy spojenými s hodnocením, včetně vysazení zakázaných léků (pokud relevantní).
    2.Věk ≥18 let v době podpisu informovaného souhlasu.
    3.Morfologicky dokumentovaná primární AML nebo AML sekundární po myelodysplastickém syndromu (MDS) dle definice uvedené v kritériích Světové zdravotnické organizace na základě patologické analýzy na pracovišti klinického hodnocení.
    4.Aktuálně první relaps (s délkou remise 6 měsíců nebo méně) nebo refrakterní na předchozí léčbu s HSCT nebo bez ní. Indukční terapie zahrnovala alespoň 1 cyklus anthracyklinu/mitoxantronu s indukčním blokem o standardní dávce.
    •Pojem refrakterní je definován následovně:
    -Po 1 cyklu došlo k redukci počtu blastů v kostní dřeni nižší než 50 % a nebyla dosažena CR, CRp ani CRi.
    -Po 2 cyklech nebyla dosažena CR, CRp ani CRi.
    •První relaps (s délkou remise 6 měsíců nebo méně) je definován následovně:
    -Dosažení CR, CRi nebo CRp dle kritérií 2003 International Working Group (Mezinárodní pracovní skupina) po úvodní terapii AML s konsolidací nebo udržovací léčbou či bez nich a s HSCT nebo bez ní.
    -Délka CR, CRi nebo CRp se měří od data vyšetření kostní dřeně s potvrzenou odpovědí nebo data alogenní transplantace po datu vyšetření kostní dřeně, při kterém byl zjištěn relaps, nebo zjištění přítomnosti periferních blastů.
    5.Přítomnost FLT3-ITD aktivující mutace v kostní dřeni nebo periferní krvi (poměr alel dle centrální laboratoře s hraniční hodnotou ≥3 % FLT3 ITD / celkový FLT3). Pokud byl vzorek odeslán k testování FLT3-ITD v centrální laboratoři, ale subjekt vyžaduje léčbu AML dříve, než bude výsledek testu FLT3-ITD z centrální laboratoře dostupný, lze k randomizaci po konzultaci lékařského monitora použít i lokální výsledek.
    6.Pacient je dle vyhodnocení zkoušejícího vhodný pro předem zvolenou záchrannou chemoterapii.
    7.Funkční skóre ECOG 0-2.
    8.Vysazení předchozí léčby AML před zahájením hodnocené léčby (kromě hydroxyurey či jiných terapií ke kontrole leukocytózy) minimálně 2 týdny před zahájením hodnocené terapie u cytotoxických látek nebo alespoň 5 poločasů u necytotoxických látek.
    9.Sérová hladina kreatininu ≤1,5×horního limitu normy (ULN) nebo glomerulární filtrace >25 ml/min dle Cockcroft-Gaultova vzorce.
    10.Sérová hladina draslíku, hořčíku a vápníku (sérová hladina vápníku korigovaná na hypoalbuminémii) v rámci limitů normy daného pracoviště. Subjekty s hladinou elektrolytů mimo normální rozsah bude možné zařadit, pokud budou tyto hodnoty zkorigovány při opakovaném testování po potřebné suplementaci.
    11.Sérová hladina celkového bilirubinu ≤1,5×ULN.
    12.Sérová hladina aspartáttransaminázy (AST) a/nebo alanintransaminázy (ALT) ≤2,5× ULN.
    E.4Principal exclusion criteria
    Candidates will be excluded from study entry if any of the following criteria are met at screening or other specified time point:
    1.Acute promyelocytic leukemia (AML subtype M3).
    2.AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior MDS.
    3.History of another malignancy, unless the candidate has been disease-free for at least 5 years.
    •Candidates with treated non-melanoma skin cancer, carcinoma in situ, or cervical intraepithelial neoplasia are eligible regardless of the time spent disease-free, if they have completed definitive treatment.
    •Candidates with organ-confined prostate cancer, with no evidence of recurrent or progressive disease, are eligible if hormonal therapy has been begun, or if the tumor has been surgically removed or treated with definitive radiotherapy.
    4.Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.
    5.Clinically significant GVHD or GVHD requiring initiation of treatment or treatment escalation within 21 days, and/or > Grade 1 persistent or clinically significant non hematologic toxicity related to HSCT.
    6.History of or current, central nervous system involvement with AML.
    7.Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
    8.Prior treatment with quizartinib or participated in a prior quizartinib study.
    9.Prior treatment with a FLT3 targeted therapy including sorafenib or investigational FLT3 inhibitors.
    10.Major surgery within 4 weeks prior to screening.
    11.Radiation therapy within 4 weeks prior to screening.
    12.Uncontrolled or significant cardiovascular disease, including:
    •QTcF interval >450 msec (average of triplicate determinations).
    •Subject has bradycardia of less than 50 BPM (as determined by central reading) unless the subject has a pacemaker.
    •Diagnosed or suspected long QT syndrome, or known family history of long QT syndrome.
    •History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes.
    •History of second or third degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers.
    •Myocardial infarction within 6 months prior to screening.
    •Uncontrolled angina pectoris within 6 months prior to screening.
    •New York Heart Association (NYHA) Class 3 or 4 congestive heart failure.
    •Left ventricular ejection fraction (LVEF) ≤45 % or institutional lower limit of normal.
    •Uncontrolled hypertension.
    •Complete left or right bundle branch block.
    13.Active infection not well controlled by antibacterial, antifungal, and/ or antiviral therapy.
    14.Known infection with human immunodeficiency virus, or active hepatitis B or C, or other active clinically relevant liver disease.
    15.Unwillingness to receive infusion of blood products according to the protocol.
    16.In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use a highly effective contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion.
    •Male subjects must not freeze or donate sperm starting at Screening and throughout the study period and 105 days after the final study drug administration.
    17.In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion. Additionally, for women randomized to chemotherapy, unwillingness to adhere to the restrictions in the respective locally established guidelines and local approved label (prescribing information, Summary of Product Characteristics and the Patient Information Leaflet (package insert) as instructed by the Investigator.
    •Highly effective contraception methods include: hormonal methods associated with inhibition of ovulation, intra-uterine device; surgical sterilization (including partner’s vasectomy) or sexual abstinence if this is the preferred and usual lifestyle of the subject
    •Female subjects must not donate or retrieve, for their own use, ova started from the
    time of Screening and throughout the study treatment period, and for 12 weeks after the final study drug administration
    18.Pregnancy
    19.Female subjects must agree not to breastfeed from the time of Screening and throughout the study period, and for 25 days after the final study drug administration.
    20.Medical condition, serious intercurrent illness, or other circumstance that, in the Investigator’s judgment, could jeopardize the candidate’s safety as a study subject, or that could interfere with study objectives.
    21.For subjects in the UK only: Refusal of permission to allow the subject’s General Practitioner to be notified of their participation in the study.
    Kandidáti budou vyřazeni, pokud budou při screeningu nebo v jiném určeném časovém bodu splněna kterákoli z následujících kritérií:
    1.Akutní promyelotická leukémie (AML subtyp M3).
    2.AML sekundární po předchozí chemoterapii z důvodu jiných neoplázií, až na AML sekundární po MDS.
    3.Anamnéza jiné malignity; pokud se však u kandidáta onemocnění posledních 5 let neobjevilo, lze jej zařadit.
    •Kandidáti s léčenou nemelanomovou rakovinou kůže, karcinomem in situ nebo cervikální intraepiteliální neoplázií mohou být zařazeni bez ohledu na dobu bez známek onemocnění, pokud absolvovali léčbu.
    •Kandidáti s rakovinou prostaty omezenou na daný orgán bez známek rekurence nebo progresivního onemocnění jsou vhodní, pokud začali s hormonální léčbou nebo pokud byl tumor chirurgicky odstraněn nebo vyřešen radioterapií.
    4.Perzistentní klinicky významná nehematologická toxicita >stupně 1 z předchozí terapie AML.
    5.Klinicky významná GVHD nebo GVHD vyžadující léčbu či eskalaci léčby méně než 21 dnů a/nebo perzistentní či klinicky významná nehematologická toxicita >stupeň 1 spojená s HSCT.
    6.Anamnéza nebo aktuální postižení centrálního nervového systému AML.
    7.Klinicky významná abnormalita koagulace jako např. diseminovaná intravaskulární koagulace.
    8.Předchozí léčba quizartinibem nebo účast v předchozím klinickém hodnocení s quizartinibem.
    9.Předchozí léčba zaměřená na FLT3 včetně sorafenibu nebo výzkumných inhibitorů FLT3 (kromě midostaurinu).
    10.Závažný chirurgický výkon méně než 4 týdny před screeningem.
    11.Radioterapie méně než 4 týdny před screeningem.
    12.Nekompenzované nebo významné kardiovaskulární onemocnění, včetně následujících položek:
    •Interval QTcF >450 ms (průměr tří měření).
    •Subjekt má bradykardii s tepovou frekvencí nižší než 50/min, pokud subjekt nemá kardiostimulátor.
    •Diagnostikovaný nebo suspektní syndrom dlouhého QT nebo známá rodinná anamnéza syndromu dlouhého QT.
    •Anamnéza klinicky relevantních komorových arytmií, jako komorová tachykardie, komorová fibrilace nebo torsade de pointes.
    •Anamnéza atrioventrikulární blokády druhého nebo třetího stupně. Kandidáty s anamnézou atrioventrikulární blokády lze zařadit, pokud mají implantovaný kardiostimulátor, nemají anamnézu synkop nebo klinicky relevantních arytmií s kardiostimulátorem.
    •Infarkt myokardu méně než 6 měsíců před screeningem.
    •Nekompenzovaná angina pectoris méně než 6 měsíců před screeningem.
    •Městnavé srdeční selhání třídy NYHA (New-Yorská kardiologická asociace) 3 nebo 4.
    •Ejekční frakce levé komory (LVEF) ≤45 % nebo spodní limity normy pracoviště.
    •Nekompenzovaná hypertenze.
    •Kompletní blokáda levého nebo pravého Tawarova raménka.
    13.Aktivní infekce nedostatečně kontrolovaná antibakteriální , antifungální nebo antivirotickou léčbou.
    14.Známá infekce virem lidské imunodeficience nebo aktivní hepatitida B či C nebo jiné aktivní klinicky relevantní jaterní onemocnění.
    15.Neochota dostávat infuze krevních produktů v souladu s protokolem.
    16.Muž, jehož sexuální partnerka je plodná žena, kdy tento muž či jeho partnerka nejsou ochotni nebo schopni používat vysoce spolehlivou metodu kontroly početí v průběhu celého léčebného období hodnocení a po dobu alespoň 3 měsíců po dokončení hodnocení.
    •Subjekty mužského pohlaví nesmí mrazit ani darovat sperma od screeningu, po celou dobu hodnocení a po dobu 105 dnů po podání poslední dávky hodnoceného léku.
    17.Heterosexuálně aktivní plodná žena neochotná nebo neschopná používat vysoce spolehlivou metodu kontroly početí v průběhu celého léčebného období hodnocení a po dobu alespoň 3 měsíců po dokončení hodnocení. Kromě toho neochota nebo neschopnost u ženy randomizované do skupiny s chemoterapií dodržet omezení příslušného lokálně schváleného postupu a lokálně schváleného označení( Souhrnu údajů o přípravku, nebo USA produktového letáku) a Příbalové informace pro pacienty dle pokynů zkoušejícího.
    •Ženy nejsou považovány za plodné, pokud jsou postmenopauzální (alespoň 2 roky bez menstruace) nebo chirurgicky sterilizované (alespoň 1 rok před hodnocením).
    •Vysoce spolehlivá metoda početí zahrnuje: hormonální metoda spojená s utlumením ovulace, nitroděložní tělísko; chirurgická sterilizace (včetně partnerovy vasektomie) nebo sexuální abstinence pokud je to preferovaný a obvyklý životní styl subjektu.
    •Subjekty ženského pohlaví nesmí darovat ani uchovávat pro vlastní potřebu vajíčka od screeningu, po celé léčebné období hodnocení a po dobu 12 týdnů po podání poslední dávky hodnoceného léku.
    18.Těhotenství
    19.Subjekty ženského pohlaví musí souhlasit, že nebudou kojit od screeningu, po celou dobu hodnocení a po dobu 25 dnů po podání poslední dávky hodnoceného léku.
    20.Zdravotní stav, závažné souběžné onemocnění či jiné okolnosti, které by dle názoru zkoušejícího mohly ohrozit bezpečí kandidáta jako subjektu hodnocení nebo které by mohly interferovat s cíli hodnocení.
    21.Pouze pro subjekty v UK: Odmítnutí souhlasu s nahlášením účasti subjektu v tomto hodnocení jeho praktickému lékaři.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable is overall survival, the time from randomization until death from any cause.
    Proměnná primární účinnosti je celkové přežívání, doba od randomizace až do úmrtí bez ohledu na příčinu.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Time from enrollment of first subject to the 280th event (death) will be approximately 22 months.
    Doba od zařazení prvního subjektu do 280 události (smrti) bude přibmižně 22 měsíců.
    E.5.2Secondary end point(s)
    The secondary variable is event-free survival, the time from randomization until documented disease progression/treatment failure, relapse, or death from any cause.
    Sekundární proměnná je přežívání bez příhod, doba od randomizace do zdokumentované progrese onemocnění / selhání léčby, relapsu či úmrtí bez ohledu na příčinu.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Time from enrollment of first subject to the 280th event (death) will be approximately 22 months.
    Doba od zařazení prvního subjektu do 280 události (smrti) bude přibmižně 22 měsíců.
    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 No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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.7.1.3.1Other 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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) Yes
    E.8.2.2Placebo No
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA71
    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
    Australia
    Belgium
    Canada
    Croatia
    Czech Republic
    France
    Germany
    Hungary
    Italy
    Korea, Republic of
    Netherlands
    New Zealand
    Poland
    Serbia
    Singapore
    Spain
    Taiwan
    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
    LVLS
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months36
    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: 273
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 272
    F.4.2.2In the whole clinical trial 363
    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)
    None
    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 National Institute for Health Research Cancer Research Network (NCRN)
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-04-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-01-20
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA