Purpose: To conduct a phase 1 clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for Chronic Myelomonocytic Leukemia (CMML). Experimental Design: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an ANC<0.25x103 c/dL and a platelet count<35x103c/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5mg BID to 20mg BID of ruxolitinib in 5mg dose escalations. Results: Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher-risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose limiting toxicities for ruxolitinib were identified. One subject had Grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28-409 days). Four had hematologic improvement and one patient had a partial response per 2006 IWG criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease related-symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n=7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF dependent STAT5 phosphorylation. Conclusions: The recommended phase 2 dose of ruxolitinib is 20mg BID. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease related B-symptoms that warrants further study.
- Received November 17, 2015.
- Revision received January 5, 2016.
- Accepted January 27, 2016.
- Copyright © 2016, American Association for Cancer Research.