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    Summary
    EudraCT Number:2006-002011-27
    Sponsor's Protocol Code Number:CLBH589B2211
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-12-15
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2006-002011-27
    A.3Full title of the trial
    A phase II, multicentre study of oral LBH589 in patients with accelerated phase or blast phase (blast crisis) chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors
    A.4.1Sponsor's protocol code numberCLBH589B2211
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameLBH589B
    D.3.2Product code LBH589B
    D.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeLBH589B
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5 to 20
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    Patients with accelerated phase (AP) or blast crisis (BC) CML who have disease-resistance following treatment with at least two BCR-ABL tyrosine kinase inhibitors (i.e., imatinib, nilotinib, or dasatinib).
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.1
    E.1.2Level LLT
    E.1.2Classification code 10009015
    E.1.2Term Chronic myeloid leukemia
    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 hematologic response (complete hematologic response (CHR) / no evidence of leukemia (NEL) / return to chronic phase (RTC)) rate
    E.2.2Secondary objectives of the trial
    1. To determine the duration of the hematologic response
    2. To determine the complete cytogenetic response (CCyR) rate
    3. To determine the major (complete/partial) cytogenetic response rate
    4. To determine the overall (complete/partial/minor/minimal) cytogenetic response rate
    5. To determine the duration of complete cytogenetic response
    6. To determine the duration of major cytogenetic response
    7. To determine the major and complete molecular response rates
    8. To characterize BCR-ABL mutations of patients at study entry and, in responding patients, at the time of disease progression
    9. To estimate progression-free survival time
    10. To estimate overall survival time
    11. To characterize the population pharmacokinetics
    12. To monitor the QTc interval in patients receiving oral LBH589
    13. To evaluate the safety and tolerability profile of oral LBH589 when given at 20 mg p.o. on Mon, Wed, Fri weekly
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or female patients aged ≥ 18 years old
    • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
    • Diagnosis of Ph+ accelerated or blast phase CML defined as:
    Accelerated phase - the presence of at least one of the following:
    - ≥15% but <30% blasts in blood or bone marrow
    - ≥30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that <30% blasts present in bone marrow)
    - ≥ 20% basophiles in the peripheral blood
    - Thrombocytopenia <100 X 109 /L unrelated to therapy
    Blast phase (blast crisis) - the presence of one of the following:
    - ≥ 30% blasts in the blood, marrow or both
    - Extramedullary infiltrates of leukemic cells
    • Prior treatment with at least two BCR-ABL tyrosine kinase inhibitors (i.e., imatinib, nilotinib, or dasatinib) and demonstrated resistance to the most recent kinase inhibitor therapy.
    • Resistance to a tyrosine kinase inhibitor for eligibility into this protocol is defined as one of the following while the patient was on therapy:
    - A patient who was in chronic phase CML who had disease progression to either accelerate phase or blast crisis
    - A patient who was in accelerated phase had disease progression to blast crisis
    - Patients in AP or BC who did not achieve a hematologic response (defined as not achieving CHR, NEL or RTC) within 3 months of starting therapy
    - Patients in AP or BC who had increasing blast counts in peripheral blood or increasing marrow leukemic infiltrate (MLI, the percent marrow blasts multiplied by marrow cellularity)
    • Patients with a history of intolerance to one BCR-ABL kinase inhibitors (defined as discontinuation of treatment due grade 3 or 4 adverse events related to treatment) will be considered eligible to enter the study if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor as defined above.
    • Patients must meet special laboratory criteria (details see protocol)
    • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal
    • Patients with an ECOG Performance Status of ≤ 2
    E.4Principal exclusion criteria
    • A candidate for hematopoitic stem cell transplantation (HSCT) (i.e. patient is a candidate has an appropriate donor, and agrees to transplantation)
    • Prior treatment with an HDAC inhibitor
    • Patients who are in chronic phase (CP) CML
    • Impaired cardiac function including any one of the following:
    - Screening ECG with a QTc > 450 msec
    - Patients with congenital long QT syndrome
    - History of sustained ventricular tachycardia
    - Any history of ventricular fibrillation or torsades de pointes
    - Bradycardia defined as HR < 50 beats per minute (patients with a history of bradycardia who now have a permanent pacemaker and HR ≥ 50 bpm are eligible)
    - Patients with a myocardial infarction or unstable angina within 6 months of study entry
    - Congestive heart failure (NY Heart Association class III or IV)
    - Right bundle branch block and left anterior hemiblock (bifasicular block)
    - Uncontrolled hypertension
    • Concomitant use of drugs with a risk of possible risk of causing QTc prolongation or torsades de pointes listed in [Post-text Supplement 1 ]
    • Concomitant use of CYP3A4 inhibitors listed in [Post-text Supplement 1]
    • Concomitant use of any other anti-cancer therapy except anegrilide or hydroxyurea (see Section 6.6.7)
    • Patients with unresolved diarrhea CTCAE grade 1
    • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
    • Patients who have received chemotherapy, any investigational drugs (other than BCR-ABL tyrosine kinase inhibitors) or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
    • Patients who have received a BCR-ABL tyrosine kinase inhibitor within 1 week of first treatment with LBH589
    • Female patients who are pregnant or breast feeding, or patients of reproductive potential not using an effective method of birth control. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
    • Male patients whose sexual partners are WOCBP not using effective birth control
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy:
    • Hematologic response (CHR, NEL, RTC)
    • Cytogenetic response (complete, partial, minor, minimal)
    • Molecular response (major and complete)
    • Duration of hematologic response
    • Duration of complete cytogenetic response
    • Duration of major cytogenetic response
    • Progression free survival time
    • Overall survival time
    Safety:
    • AEs as determined by CTCAE version 3, SAEs
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA38
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee No
    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
    Patients may continue treatment with oral LBH589 until they experience e.g. unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator (for details see study protocol).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    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 years2
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-12-15. Yes
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 52
    F.4.2.2In the whole clinical trial 71
    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)
    The patients will receive the standard of care that is in place at that particular institution.
    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 Decision2007-01-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-01-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-01-29
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