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|Ref Type||Journal Article|
|Authors||Padron E, Dezern A, Andrade-Campos M, Vaddi K, Scherle P, Zhang Q, Ma Y, Balasis ME, Tinsley S, Ramadan H, Zimmerman C, Steensma DP, Roboz GJ, Lancet JE, List AF, Sekeres MA, Komrokji RS, null null|
|Title||A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML).|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2016 Aug 01|
|Abstract Text||To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML).Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) <0.25 × 10(3) cells/dL and a platelet count <35 × 10(3) 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.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 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.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. Clin Cancer Res; 22(15); 3746-54. ©2016 AACRSee related commentary by Solary, p. 3707.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||myelodysplastic/myeloproliferative neoplasm||not applicable||Ruxolitinib||Phase I||Actionable||In a Phase I trial, Jakafi (ruxolitinib) treatment demonstrated safety and preliminary efficacy in chronic myelomonocytic leukemia patients, resulted in a total response rate of 35% (7/20) and reduction of Stat5 signaling (PMID: 26858309).||26858309|