A Phase I, Dose-finding Study of BEZ235 in Adult Patients With Relapsed or Refractory Acute Leukemia

Summary

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

Timeline

Start

2012-06

Primary completion

2017-12

Completion

2020-02-07

Publications

• Lang F, Wunderle L, Badura S, Schleyer E, Bruggemann M, Serve H, Schnittger S, Gokbuget N, Pfeifer H, Wagner S, Ashelford K, Bug G, Ottmann OG. A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia. BMC Pharmacol Toxicol. 2020 Sep 29;21(1):70. doi: 10.1186/s40360-020-00446-x.

Drugs

Indications