A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia

作者：Hillmen Peter^*; Cohen Dena R; Cocks Kim; Pettitt Andrew; Sayala Hazem A; Rawstron Andy C; Kennedy Daniel B; Fegan Christopher; Milligan Don W; Radford John; Mercieca Jane; Dearden Claire; Ezekwisili Raphael; Smith Alexandra F; Brown Julia; Booth Gillian A; Varghese Abraham M; Pocock Christopher

来源：British Journal of Haematology, 2011, 152(5): 570-578.

DOI：10.1111/j.1365-2141.2010.08317.x

• chronic lymphocytic leukaemia
• rituximab
• fludarabine
• cyclophosphamide
• mitoxantrone
• phase II study
• minimal residual disease

P>Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as < 0 center dot 01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.

• 出版日期2011-3