Phase I study of obatoclax mesylate (GX15-070), a small molecule pan–Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia

摘要: Obatoclax mesylate is a small molecule pan-Bcl-2 antagonist with in vitro activity against chronic lymphocytic leukemia (CLL) cells. was administered to patients advanced CLL at doses ranging from 3.5 14 mg/m(2) as 1-hour infusion and 20 40 3-hour every 3 weeks. Twenty-six received total of 74 cycles. Dose-limiting reactions were neurologic (somnolence, euphoria, ataxia) associated the infusion. The maximum tolerated dose (MTD) 28 over hours One (4%) 26 achieved partial response. Patients anemia (3/11) or thrombocytopenia (4/14) experienced improvements hemoglobin platelet counts. Circulating lymphocyte counts reduced 18 median reduction 24%. Overall, plasma concentration (C(max)) area under curve (AUC) values obatoclax proportional. Activation Bax Bak demonstrated peripheral blood mononuclear cells, induction apoptosis related overall exposure, monitored by oligonucleosomal DNA/histone complexes. has biologic modest single-agent heavily pretreated CLL. Further evaluation less combination other therapeutic agents warranted. This trial been registered http://clinicaltrials.gov identifier NCT00600964.