The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients $60 years with FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort. Fifty-four patients with a median age of 67 years (range, 60.3-82.7 years) were enrolled; 39 were FLT3-ITD patients (71%) and 15 were FLT3-TKD (29%) patients. The observed 1-year OS (95% confidence interval [CI]) was 62% (45%-78%) for the FLT3-ITD patients (meeting the primary end point 62% vs 30% for a historical control group, P, .0001) and 71% (42%-92%) for the FLT3-TKD patients. The median disease-free survival and OS were 12.2 months (95% CI, 5-16.9) and 15.0 months (95% CI, 10.4-20.1), respectively, in the FLT3-ITD group and 9.6 (95% CI, 1.9 to not available [NA]) and 16.2 months (95% CI, 5.0 to NA) for the FLT3-TKD group. This study suggests that the addition of sorafenib to chemotherapy for FLT3-ITD AML is feasible and may improve the survival of older adults with FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT01253070.