Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study

Br J Haematol. 2015 Jun;169(5):672-82. doi: 10.1111/bjh.13338. Epub 2015 Mar 2.

Abstract

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.

Keywords: CCR4; adult T-cell leukaemia-lymphoma; antibody therapy; mogamulizumab; randomized phase II study.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Female
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / mortality
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Male
  • Middle Aged
  • Nitrosourea Compounds / adverse effects
  • Nitrosourea Compounds / therapeutic use
  • Prednisolone / adverse effects
  • Prednisolone / therapeutic use
  • Treatment Outcome
  • Vincristine / adverse effects
  • Vincristine / therapeutic use
  • Vindesine / adverse effects
  • Vindesine / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Nitrosourea Compounds
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Prednisolone
  • Carboplatin
  • Vindesine
  • mogamulizumab

Supplementary concepts

  • LSG15 regimen

Associated data

  • ClinicalTrials.gov/NCT01173887