慢性淋巴细胞白血病(CLL)是最常见的成人白血病。联合免疫化学疗法如氟达拉滨,环磷酰胺和利妥昔单抗是适合患者的标准一线治疗,但关于患者复发后的最佳治疗的证据有限.Ofatumumab作为单一疗法已被证明是有效的治疗复发,耐火CLL,因为它没有骨髓毒性,是联合化疗的理想药物。然而,目前尚不清楚Ofatumumab的最佳剂量.在复发性CLL(COSMIC)试验中,标准或Mega剂量的化疗加Ofatumumab将评估标准和高(大)剂量的Ofatumumab联合苯达莫司汀或氟达拉滨和环磷酰胺的组合的疗效和安全性,如果是,时间表应该进展到III期试验.
COSMIC是第二阶段,多中心,随机化,打开,针对以氟达拉滨为基础的化疗不耐药的复发CLL患者的平行组试验.参与者将被随机分配接受标准剂量或大剂量ofatumumab。两种剂量将与苯达莫司汀或氟达拉滨和环磷酰胺化疗骨架联合给予。主要目标是评估使用两个治疗组(大型与标准)治疗后达到完全缓解的参与者比例。治疗后3个月评估。将独立评估治疗组,以确定相对于预先指定的标准,反应水平是否可接受。如果两个治疗组都显示出可接受的反应水平,选择标准将用于确定哪种标准可用于验证性III期试验.关键的次要目标是评估复发性疾病中微小残留病(MRD)水平的动态。计划从英国的18个研究中心招募82名参与者。
目前关于复发或难治性CLL患者的最佳治疗的证据有限。因此迫切需要合适的治疗方法。COSMIC试验将确定Ofatumumab联合化疗在该人群中是否安全有效,并将确定进一步研究的最佳剂量。
ISRCTN51382468。2011年9月21日注册。
Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as monotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic, it is an ideal drug to combine with chemotherapy. However, the optimal dose of ofatumumab in this setting is not known. The Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial will assess the efficacy and safety of standard and high (mega) doses of ofatumumab combined with bendamustine or a combination of fludarabine and cyclophosphamide to determine which, if either, schedule should progress to a phase III trial.
COSMIC is a phase II, multi-centre, randomised, open, parallel group trial for patients with relapsed CLL who are not refractory to fludarabine-based chemotherapy. Participants will be randomised to receive either standard dose or mega dose ofatumumab. Both doses will be given in combination with either bendamustine or fludarabine and cyclophosphamide chemotherapy backbone. The primary objective is to assess the proportion of participants achieving a complete remission following therapy with the two treatment arms (mega versus standard), as assessed at 3 months post treatment. The treatment groups will be assessed independently to determine whether the level of response is acceptable in relation to pre-specified criteria. If both treatment groups show an acceptable level of response, selection criteria will be used to determine which to take forward to a confirmatory phase III trial. A key secondary objective is to assess the dynamics of minimal residual disease (MRD) levels in relapsed disease. Eighty-two participants are planned to be recruited from 18 research centres in the UK.
Currently there is limited evidence regarding the optimal treatment of patients with relapsed or refractory CLL, and so suitable therapies are urgently needed. The COSMIC trial will identify whether ofatumumab given in combination with chemotherapy is safe and effective in this population, and will identify the optimal doses for further investigation.
ISRCTN51382468 . Registered on 21 September 2011.