The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.
Name: Nilotinib + LDE225
Description: Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.Type: DrugNilotinib + LDE225
Description: Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225
Measure: Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy Time: 56 days (2 treatment cycles at 28 days each)Description: Assessment of the safety and tolerability profile of nilotinib in combination with LDE225
Measure: No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms Time: 336 days (12 treatment cycles)Description: Assessment of the PK characteristics of nilotinib administered in combination with LDE225
Measure: Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC) Time: 50 daysDescription: Determination of the kinetics of major molecular response
Measure: Major molecular response (MMR) rates at 3, 6 and 12 months Time: 336 days (12 treatment cycles)Description: Determination of the kinetics of complete molecular response
Measure: Complete molecular response (CMR) rates at 3, 6 and 12 months Time: 336 days (12 treatment cycles)Description: Determination of major cytogenetic response rates
Measure: Major cytogenic response (MCyR) rates by 3, 6 and 12 months Time: 336 days (12 treatment cycles)Description: Determination of complete cytogenetic response rates
Measure: Complete cytogenic response (CCyR) rates by 3, 6 and 12 months Time: 336 days (12 treatment cycles)Single Group Assignment
There are 4 SNPs
Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K ---
Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K --- --- T315I --- --- F359C ---
Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K --- --- T315I ---
Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H ---