Primary objectives: - To establish the maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D) of BEZ235 when administered twice daily (BID) as a single agent in patients with relapsed or refractory acute leukemia - To determine the dose-limiting toxicity (DLT) Secondary objectives: - Assess the safety and tolerability of daily oral administration of BEZ235 with a BID schedule - To describe preliminary anti-leukemic activity of BEZ235 in patients with acute leukemia - To correlate changes in pharmacodynamic biomarkers with basic pharmacokinetic data Exploratory objectives: - To assess pre-treatment phosphatidylinositol 3-kinase (PI3K) pathway-related genes in blast cells and all other malignant cells derived from blood or bone marrow. - To assess the pharmacodynamic changes in components of the PI3K-protein kinase B (AKT)-mTOR pathway in bone marrow following treatment as potential predictive biomarkers of pharmacodynamic (PD) activity of BEZ235 in association with clinical responses. - To identify potential resistance mechanisms and biomarkers that may correlate with efficacy and response from blood and bone marrow samples pre-and post-treatment in case of resistance
Name: BEZ235
Allocation: N/A
Single Group Assignment
There is one SNP
If a point mutation threonine 315 to isoleucine (T315I) bcr-abl mutation has been identified, prior treatment with a second TKI is not required. --- T315I ---
or: 3. Patients with Philadelphia chromosome and/or bcr-abl positive B-precursor ALL or prior CML-BP with presence of minimal residual disease (MRD) and the presence of T315I mutation or a high-resistance mutation shown to be unresponsive to approved thyrosine kinase inhibitors (TKI). --- T315I ---