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
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the hematologic response (complete hematologic response (CHR) / no evidence of leukemia (NEL) / return to chronic phase (RTC)) rate ;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 ;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 | — |
Countries
Belgium, Denmark, France, Germany, Italy, Netherlands
Outcome results
None listed