Browsing The Christie Research Publications Repository by Authors
Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia.O'Brien, S; Rizzieri, D; Vey, N; Ravandi, F; Krug, U; Sekeres, M; Dennis, Michael; Venditti, A; Berry, D; Jacobsen, T; et al. (2012-09)Elacytarabine is a novel cytotoxic nucleoside analogue, independent of nucleoside transporters (e.g. human Equilibrative Nucleoside Transporter 1 [hENT1]) for cell uptake, and mechanisms of action similar to those of cytarabine. This Phase II study assessed the efficacy and safety of elacytarabine in patients with advanced stage acute myeloid leukaemia (AML). Patients received 2000 mg/m(2) per d continuously i.v. during days 1-5 every 3 weeks. Patients were matched by six risk factors with historical controls; remission rate (assessed after 1 or 2 cycles) and 6-month survival were compared. Sixty-one patients, median age 58 years, were enrolled; 52% had five or six risk factors. The remission rate was 18% (95% confidence interval: 9-30%) vs. 4% in controls (P < 0·0001), 6-month survival rate was 43%, median overall survival was 5·3 months (vs. 1·5 months); 10 patients (16%) were referred for stem cell transplantation after treatment. Side effects were predictable and manageable. The most common grade 3/4 non-haematological adverse events were febrile neutropenia, hypokalemia, fatigue, hyponatraemia, dyspnoea and pyrexia. Thirty-day all-cause mortality, after start of treatment, was 13% vs. 25% in controls. Elacytarabine has monotherapy activity in patients with advanced AML. This study provides proof-of-concept that lipid esterification of nucleoside analogues is clinically relevant.
Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.Byrd, J; Brown, J; O'Brien, S; Barrientos, J; Kay, N; Reddy, N; Coutre, S; Tam, C; Mulligan, S; Jaeger, U; et al. (2014-07-17)In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome.
Improvement in parameters of hematologic and immunologic function and patient well-being in the phase III RESONATE study of Ibrutinib versus ofatumumab in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma.Barrientos, J; O'Brien, S; Brown, J; Kay, N; Reddy, N; Coutre, S; Tam, C; Mulligan, S; Jaeger, U; Devereux, S; et al. (2018-08-18)Ibrutinib compared with ofatumumab significantly improves progression-free and overall survival in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).