Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis

PRIMARY OBJECTIVE: I. To obtain preliminary evidence of the efficacy of elotuzumab in patients with myelofibrosis (MF) by estimating the rate of overall response by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria. SECONDARY OBJECTIVES: I. To characterize the safety and tolerability of elotuzumab in patients with MF. II. To assess for improvements in cytopenias and bone marrow fibrosis grade, splenomegaly and disease-related symptoms. III. To determine the duration of objective responses, if any, to elotuzumab. IV. To determine the time to next treatment. EXPLORATORY OBJECTIVES: I. To assess the proportion of circulating monocytes expressing the target of elotuzumab, SLAMF7, and any correlation of the same to the mutant JAK2 allele burden. II. To assess baseline levels of IL-1Ralpha and other cytokines and the effects of elotuzumab, if any, on these over time. III. To examine the effects of elotuzumab on fibrocyte count and differentiation, both in vitro and in vivo. IV. To assess clonal evolution, if any, in MF patients on elotuzumab treatment. OUTLINE: Patients receive elotuzumab intravenously (IV) over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then periodically thereafter.