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    The EU Clinical Trials Register currently displays   31553   clinical trials with a EudraCT protocol, of which   5083   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2014-003065-15
    Sponsor's Protocol Code Number:WO29519
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-01-04
    Trial 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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-003065-15
    A.3Full title of the trial
    A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PHASE III STUDY OF IDASANUTLIN, AN MDM2 ANTAGONIST, WITH CYTARABINE VERSUS CYTARABINE PLUS PLACEBO IN PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Idasanutlin with Cytarabine versus Cytarabine plus Placebo in Patients with Relapsed or Refractory Acute Myeloid Leukemia.
    A.4.1Sponsor's protocol code numberWO29519
    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 SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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/3/14/1328
    D.3 Description of the IMP
    D.3.1Product nameidasanutlin
    D.3.2Product code RO5503781/F13-01
    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 INNidasanutlin
    D.3.9.1CAS number 1229705-06-9
    D.3.9.2Current sponsor codeRO5503781
    D.3.9.4EV Substance CodeSUB167603
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 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.2.1.1.1Trade name CYTARABINE
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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
    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.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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
    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
    Relapsed or refractory acute myeloid leukemia (AML).
    E.1.1.1Medical condition in easily understood language
    Acute myeloid leukemia is a type of blood cancer. This cancer starts in the blood-forming cells of the bone marrow and is characterised by an over-production of immature white 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 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
    Within the TP53 wild-type population:
    • To compare overall survival (OS) in patients with relapsed or refractory AML who have been randomized to idasanutlin in combination with cytarabine versus those who have been randomized to cytarabine and placebo.
    E.2.2Secondary objectives of the trial
    Within the all-patient population
    • To compare OS in patients with relapsed or refractory AML who have been randomized to idasanutlin in combination with cytarabine versus those who have been randomized to cytarabine and placebo.
    Within the all-patient population and the TP53 wild-type population
    • To compare
    - the proportions of complete remission (CR), and CR with incomplete platelet count recovery (CRp) between treatment arms
    - the proportions of overall remissions (CR, CRp, CR with incomplete blood count recovery [CRi]) between treatment arms
    - event-free survival (EFS) and leukemia-free survival (LFS) between treatment arms
    - the proportions of allogeneic hematopoietic stem cell transplant (HSCT) following response between treatment arms
    - the differences in disease and treatment related symptoms and health related quality of life
    • To assess the safety between treatment arms
    • To characterize the pharmacokinetics of both idasanutlin and cytarabine.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age >=18 years
    - Documented/confirmed 1st/2nd refractory/relapsed AML using World Health Organization classification, except acute promyelocytic leukemia and first relapsed AML patients with a CR1 duration of >1 year AND age <60 years.
    - No more than 2 prior induction regimens (excl. prior HSCT) in their first line treatment and one must have included cytarabine with an anthracycline (or anthracenedione)
    - Eastern Cooperative Oncology Group performance status of 0 to 1
    - Adequate hepatic and renal function.
    - WBC count at randomization of <=50,000/cubic millimeter (mm3).
    E.4Principal exclusion criteria
    - First relapsed patients aged < 60 years with a CR1 duration of > 1 year
    - Patients with prior documented antecedent hematological disorder (AHD)
    - AML secondary to any prior chemotherapy unrelated to leukemia
    - Patients who are either refractory to/or relapsed within 90 days of receiving a regimen containing a cumulative dose of >=18 gram/square meter cytarabine
    - Patients who have received allogeneic HSCT within 90 days prior to randomization
    - Patients who have received immunosuppressive therapy for graft versus host disease within 2 weeks prior to randomization
    - Prior treatment with a Murine Double Minute 2 (MDM2) antagonist
    - Patients with clinically relevant QTc prolongation (QTcF > 480 ms), a family history of long QT syndrome, or who are currently receiving treatment with medications that are known to prolong the QT interval
    - Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 30 days from the first receipt of study drug with the exception of HU or leukapheresis in patients who need to continue this therapy to maintain a WBC count <=50000/mm3. HU or leukapheresis must be discontinued at least 24 hours prior to the initiation of study medication
    - Patients with acute toxicities from any prior anti-leukemia therapy that have not resolved to Grade <=2 per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE), Version 4.03
    - Patients with a history of other malignancy within 5 years prior to screening
    - Patients unable to temporarily interrupt treatment with moderate to strong CYP2C8 inducers and inhibitors (including gemfibrozil, which is also an inhibitor of UGT1A3), CYP2C8 or OATP1B1/3 substrates, or strong CYP3A4 inducers during the treatment phase. These agents must be discontinued 7-14 days prior to the start of study medication
    - Patients unable to temporarily interrupt treatment with oral or parenteral anticoagulants/anti-platelet agents (e.g., warfarin, chronic daily treatment with aspirin [> 325 mg/day], clopidogrel, dabigatran, apixaban, rivaroxaban, or subcutaneous [SC] anticoagulant prophylaxis) during the treatment phase. These agents must be discontinued 7 days (or 5 half-lives) prior to the start of study medication
    - Patients with a history of systemic hypersensitivity reactions >=Grade 2 attributed to cytarabine
    - Patients who have any severe and/or uncontrolled medical conditions or other conditions that could impair the ability of the investigator to evaluate the patient, or impair the patient's ability to complete the study
    - Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the patient upon the induction of neutropenia, that is, patients who are or should be on antimicrobial agents for the treatment of active infection
    - Patients with extramedullary AML with no evidence of systemic involvement
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival (OS) in TP53 wild-type population.
    E.5.1.1Timepoint(s) of evaluation of this end point
    - Interim analysis, after 120 patients enrolled
    - primary analysis, approximately 4.5 years after study start.
    E.5.2Secondary end point(s)
    1. OS in the all-patient population
    2. CR and CRp proportions at the end of induction in the TP53 wild-type population
    3. Overall remission rate (ORR) (CR, CRp and CRi) proportion at the end of induction in the TP53 wild-type population
    4. EFS in the TP53 wild-type population
    5. LFS in the TP53 wild-type population
    6. Proportion of HSCT in the TP53 wild-type population 7. CR and CRp proportions at the end of induction in the overall population
    8. ORR (CR, CRp and CRi) proportion at the end of induction in the overall population
    9. EFS in the overall population
    10. LFS in the overall population
    11. Proportion of HSCT in the overall population.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Interim analysis, after 120 patients enrolled
    - primary analysis, approximately 4.5 years after study start.
    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 No
    E.6.4Safety Yes
    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 No
    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 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 EEA56
    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
    Austria
    Belgium
    Canada
    Finland
    France
    Germany
    Israel
    Italy
    Korea, Republic of
    Netherlands
    New Zealand
    Norway
    Russian Federation
    Spain
    Switzerland
    United Kingdom
    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'
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months6
    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: 176
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 264
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 338
    F.4.2.2In the whole clinical trial 440
    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
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-01-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-05-18
    P. End of Trial
    P.End of Trial StatusOngoing
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