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    Summary
    EudraCT Number:2012-005124-15
    Sponsor's Protocol Code Number:CAMN107AIC05
    National Competent Authority:Croatia - MIZ
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-09-04
    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 ConcernedCroatia - MIZ
    A.2EudraCT number2012-005124-15
    A.3Full title of the trial
    A prospective, randomized, open label two arm Phase III study to evaluate treatment free remission (TFR) rate in patients with Philadelphia-positive CML after two different durations of consolidation treatment with nilotinib 300mg BID.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical research study evaluating the possibility to suspend the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients who have been for two different durations on Tasigna with a predifined level of molecular response.
    A.3.2Name or abbreviated title of the trial where available
    ENESTpath
    A.4.1Sponsor's protocol code numberCAMN107AIC05
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01743989
    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 SponsorNovartis Pharma Services AG
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAltiora
    B.5.2Functional name of contact pointDenis Brkic
    B.5.3 Address:
    B.5.3.1Street AddressSeferova 8
    B.5.3.2Town/ cityZagreb
    B.5.3.3Post code10040
    B.5.3.4CountryCroatia
    B.5.6E-maildenis.brkic@altiora-cro.net
    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 Yes
    D.2.1.1.1Trade name Tasigna
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/3/06/375
    D.3 Description of the IMP
    D.3.1Product namenilotinib
    D.3.2Product code AMN107
    D.3.4Pharmaceutical form Capsule, hard
    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 INNNILOTINIB
    D.3.9.1CAS number 641571-10-0
    D.3.9.2Current sponsor codeAMN107
    D.3.9.4EV Substance CodeSUB25225
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    Adult patients with Ph+ chronic phase CML that have been treated with Imatinib for at least 2 years, are in CCyR, but have not achieved MR4.0 at study entry.
    E.1.1.1Medical condition in easily understood language
    Adult patients with CML who have been treated with imatinib (Glivec) for at least two years and who have not achieved a certain level of molecular response at study entry.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10054352
    E.1.2Term Chronic phase chronic 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
    To assess the optimal duration of consolidation treatment with nilotinib 300 mg BID in order that patients remain in treatment free remission (≥MR4.0) without molecular relapse 12 months after cessation of nilotinib.
    E.2.2Secondary objectives of the trial
    - To evaluate the proportion of patients who are eligible to suspend nilotinib therapy by achieving and maintaining a sustained ≥MR4.0 for at least 12 months during consolidation treatment with nilotinib 300 mg BID.
    - To assess the kinetics of the molecular response in patients during induction/consolidation treatment with nilotinib 300 mg BID.
    - To assess the kinetics of the molecular response in patients during the TFR phase of the study in the two treatment arms.
    - To assess the progression-free survival (PFS) rate during the TFR phase of the study in the two treatment arms.
    - To assess treatment-free survival (TFS) during the TFR phase of the study in the two treatment arms.
    - To assess the overall survival (OS) rate during the TFR phase of the study in the two treatment arms.
    - To assess the safety profile of nilotinib during the induction/consolidation treatment phase, the TFR phase, and during the treatment re-initiation phase.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients eligible for inclusion in this study have to meet all of the following criteria:

    •Confirmed diagnosis of chronic phase Ph+ CML
    •Previous first-line treatment with imatinib for a minimum of 2 years;
    •Patient in complete cytogenetic response;

    Additional inclusion criteria as per protocol apply.
    E.4Principal exclusion criteria
    Patients eligible for this study must not meet any of the following criteria:

    •Previous achievement of MR4.0 at study entry;
    •Previous treatment with other target cells inhibitors other than imatinib;
    •Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;
    •Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;
    •Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol;
    •History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively;
    •Patients who have not recovered from prior surgery;
    •Treatment with other investigational agents within 4 weeks of Day 1;
    •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.

    Additional exclusion criteria as per protocol apply.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the number of patients who remain in treatment free remission (≥MR4.0) ,without molecular relapse, at the end of 12 months in the TFR phase of the study, in the nilotinib 12 months consolidation treatment arm (arm 1) versus the nilotinib 24 months consolidation treatment arm (arm 2).
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months after treatment cessation
    E.5.2Secondary end point(s)
    - The proportion of patients who have achieved a sustained ≥MR4.0 (defined as having 4 out of 5 quarterly assessments of ≥MR4.0 by a EUTOS standardized laboratory over the last 12 months and the last assessment before randomization is at least MR4.0) during the consolidation treatment phase of the study.
    - The proportion of patients who achieve MR4.0 or MR4.5 on the study at selected time points during the induction/consolidation phase of the study.
    - The proportion of patients who maintain in MR4.0 or MR4.5 on the study at selected time points during the TFR phase in each one of the two treatment arms
    - PFS defined as progression to AP/BP or death, where the "failure" event is the earliest occurrence of either of these events; Kaplan-Meier (KM) estimation of PFS is measured from the date of start of the nilotinib TFR phase to the date of the earliest failure event. Patients not known to have recurred or died on or before the cut-off date for the KM analysis will have their PFS interval censored at the earlier of the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who are still on study, and at the date of last contact for patients who are in follow-up.
    - TFS is defined as lack of any of the following events: loss of MMR, confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BP, or death from any cause;KM estimation of TFS, which is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BP, or death from any cause.
    - Overall survival is defined as the time from start of the TFR phase to the time of death due to any cause. For patients without any event on or before the cut-off date, survival time will be censored at the date of their last assessment for patients who are still on study, and at the date of last contact for patients who are in follow-up.
    - Descriptive statistics on adverse events, laboratory abnormalities and clinically notable ECG and other safety parameters during the study
    E.5.2.1Timepoint(s) of evaluation of this end point
    see under secondary endpoints
    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 No
    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
    evaluation of treatment free remission rate
    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 No
    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) No
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA301
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years6
    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: 758
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 300
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1058
    F.4.2.2In the whole clinical trial 1058
    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)
    Patients will be treated with Standard of Care.
    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 Decision2014-04-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-03-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-07-08
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