This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti‐ CC chemokine receptor 4 antibody, to mLSG15, a dose‐intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma ( ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (% CR); secondary endpoints included the overall response rate ( ORR) and safety. The % CR and ORR in the mLSG15‐plus‐mogamulizumab arm ( n = 29) were 52% [95% confidence interval ( CI), 33–71%] and 86%, respectively; the corresponding values in the mLSG15 arm ( n = 24) were 33% (95% CI, 16–55%) and 75%, respectively. Grade ≥ 3 treatment‐emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15‐plus‐mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15‐plus‐mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher % CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.