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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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19 March 2012 |
Main ID: |
EUCTR2006-002011-27-DE |
Date of registration:
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19/01/2007 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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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
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Scientific title:
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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 |
Date of first enrolment:
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09/03/2007 |
Target sample size:
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71 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002011-27 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: no
Randomised: no
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
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Phase:
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Countries of recruitment
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Belgium
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Denmark
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France
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Germany
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Italy
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Netherlands
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Key inclusion & exclusion criteria
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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 peripheral blood or bone marrow - =30% blasts + 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 sole therapy Blast phase (blast crisis) - the presence of one of the following: - = 30% blasts in the blood, bone marrow or both - Extramedullary infiltrates of leukemic cells • Prior treatment with at least 2 BCR-ABL tyrosine kinase inhibitors (including imatinib and another BCR-ABL TKI (such as nilotinib, dasatinib, etc) and demonstrate 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 inhibitor will be considered eligible to enter the study if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor as defined above. Intolerance is defined as discontinuation of treatment due to either grade 3 or 4 adverse events related to treatment, or grade 2 adverse events related to treatment that persist for =one month or that recurs for more than 3 times despite dose reduction • Patients must also 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
Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
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 for the treatment of CML • 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 (NYHA class III or IV) - Right bundle branch block and left anterior hemiblock (bifasicular block) - Uncontrolled hypertension • Concomitant use of drugs with a risk of causing QTc prolongation or torsades de pointes, see section 6.6.8 • Concomitant use of CYP3A4/5 inhibitors, see section 6.6.8 • 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 would need to receive valproic acid for any reason during the study or = 5 days prior to starting study drug • Patients who have received chemotherapy = 3 weeks or who have not recovered from side effects of such therapy • Patients who have received immunotherapy = 1 week prior to starting study drug or who have not recovered from side effects of such therapy • Patients who have received any investigational drug = 2 weeks (or within 5 half-lives of the investigational agent or active metabolites) prior to starting study drug or who have not recovered from side effects of such therapy • Patients who have undergone major surgery = 3 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 willing to use a double methode of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment. 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 willing to use a double methode of contraception including condom during the study and 3 months after the end of treatment.
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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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 version: 8.1
Level: LLT
Classification code 10009015
Term: Chronic myeloid leukemia
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Intervention(s)
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Product Name: LBH589 Product Code: LBH589 Pharmaceutical Form: Capsule, hard Current Sponsor code: LBH589 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20-
Product Name: LBH589 Product Code: LBH589 Pharmaceutical Form: Capsule, hard Current Sponsor code: LBH589 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5-
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Primary Outcome(s)
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Secondary Objective: 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
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Main Objective: To assess the hematologic response (complete hematologic response (CHR) / no evidence of leukemia (NEL) / return to chronic phase (RTC)) rate
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Primary 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
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Secondary ID(s)
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2006-002011-27-BE
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CLBH589B2211
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Source(s) of Monetary Support
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Results
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Results available:
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