An Open-Label Phase 2 Study of Ofatumumab (Arzerra) in Combination With Oral GSK2110183 in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL)

Detailed Summary

This is a phase 2, open-label, single institution trial of combination of intravenous (IV) ofatumumab and oral GSK2110183 in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL). Patients must have received at least one prior line of therapy containing fludarabine (single-agent or combination therapy). During the initial 6 months Treatment Phase, ofatumumab will be administered weekly for 8 doses, then once every 4 week cycle for an additional 4 doses (dose and schedule identical to the pivotal phase 2 trial) and GSK2110183 will be given daily PO (Treatment Phase). There will be an initial 10 day lead-in with GSK2110183 alone prior to initiation of ofatumumab to allow for evaluation of changes in cell surface expression due to GSK2110183 and for GSK2110183 pharmacokinetic studies (Lead-in Phase). The official Cycle 1 Day 1 will start on the date of first dose of ofatumumab. Cycle duration = 4 weeks. Patients will be assessed for safety, disease assessment, response, and survival on day 1 of each cycle during the Treatment Phase. A formal review of safety data by the Data Safety Monitoring Board (DSMB) after the first 6 patients have completed cycle 1 of the Treatment Phase will be performed before continuing accrual. All patients achieving SD, PR or CR by the end of the Treatment Phase will proceed to the Maintenance Phase. Patients with PD at any time, including by the end of Treatment Phase, will be taken off study. During the Maintenance Phase, single-agent GSK2110183 will be administered daily for a maximum of 12 months (12 cycles). Maximum duration on any study drug is 18 months (18 cycles). During the Follow-up Phase, patients will be assessed for safety, disease assessment, response, and survival every 3 months through month 36 (year 3), or until subsequent CLL therapy or death, whichever comes first. Key indications for study withdrawal are progressive disease, intolerable toxicity, or completion of therapy

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Interventions