A multi-institution phase i trial of ruxolitinib in patients with chronic myelomonocytic leukemia (CMML)

Eric Padron, Amy Dezern, Marcio Andrade-Campos, Kris Vaddi, Peggy Scherle, Qing Zhang, Yan Ma, Maria E. Balasis, Sara Tinsley, Hanadi Ramadan, Cassandra Zimmerman, David P. Steensma, Gail J. Roboz, Jeffrey E. Lancet, Alan F. List, Mikkael A. Sekeres, Rami S. Komrokji

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Purpose: To conduct a phase I 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 absolute neutrophil count (ANC) <0.25 × 103 cells/dL and a platelet count <35 × 103 cells/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg 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 doselimiting 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 International Working Group (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 II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study.

Original languageEnglish (US)
Pages (from-to)3746-3754
Number of pages9
JournalClinical Cancer Research
Issue number15
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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