%0 Clinical Trial, Phase II
%T Phase 2 study of combination chemotherapy with bortezomib in children with relapsed and refractory acute lymphoblastic leukemia.
%A Miyagawa N
%A Goto H
%A Ogawa A
%A Kikuta A
%A Kosaka Y
%A Sekimizu M
%A Tomizawa D
%A Toyoda H
%A Hiramatsu H
%A Hara J
%A Mochizuki S
%A Nakayama H
%A Yoshimura K
%A Iijima-Yamashita Y
%A Sanada M
%A Ogawa C
%J Int J Hematol
%V 118
%N 2
%D 2023 Aug 1
%M 37127801
%F 2.319
%R 10.1007/s12185-023-03609-8
%X Treatment outcomes for children with relapsed and refractory acute lymphoblastic leukemia (R/R-ALL) remain poor, and the optimal induction therapy has not been determined. Bortezomib is a proteasome inhibitor that acts synergistically and additively with standard chemotherapy for ALL. We evaluated the efficacy and safety of combination chemotherapy with bortezomib in children with R/R-ALL. This single-arm, multicenter, phase 2 study was conducted in Japan between 2016 and 2020. Eligible patients were divided into two cohorts: a high-risk first-relapse cohort of untreated patients with high-risk first-relapsed ALL and an expansion cohort of patients with refractory ALL, including multiple relapses, relapse after allogeneic hematopoietic cell transplantation, and induction failure. All patients received a single course of chemotherapy as induction therapy. Sixteen patients (10 in the high-risk first-relapse cohort, six in the expansion cohort) were evaluable. The overall remission rate after induction therapy was 60% in the high-risk first-relapse cohort and 16.7% in the expansion cohort. All patients had minimal residual disease. Adverse events were acceptable except for interstitial lung disease and hypoxia in a patient in the expansion cohort, but addition of bortezomib to conventional chemotherapy did not produce obvious improvement in children with R/R-ALL.