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 - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-002011-27-IT
• Date of registration: 18/05/2007
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: 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 - ND
• Scientific title: 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 - ND
• Date of first enrolment: 11/12/2006
• Target sample size: 71
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002011-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Belgium, Denmark, France, Germany, Italy, Netherlands

Key inclusion & exclusion 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 <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 an BCR-ABL kinase inhibitor(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 the following laboratory criteria: ? Serum albumin > 3g/dL ? AST/SGOT and ALT/SGPT <=2.5 x upper limit of normal (ULN) ) or <= 5.0 x ULN if the transaminase elevation is due to leukemic involvement ? Serum bilirubin <=1.5 x ULN ? Serum creatinine <= 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min ? Serum potassium >= LLN ? Serum phosphorus >=LLN ? Total calcium (corrected for serum albumin) or ionized calcium >= LLN ? Serum magnesium >= LLN ? TSH and free T4 WNL (patients may be on thyroid hormone replacement) ? 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 ? 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

accelerated phase or blast crisis chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors.
MedDRA version: 9.1 Level: LLT Classification code 10009013 Term: Chronic myeloid leukaemia

Intervention(s)

Product Code: LBH589
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LBH589
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Code: LBH589
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LBH589
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: 1. 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): Hematologic response

Secondary ID(s)

CLBH589B2211

2006-002011-27-BE