A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART).

Kota Kawabata; Fumiharu Ohka; Ryuta Saito; Tsuyoshi Onoe; Hideyuki Harada; Takashi Sasayama; Hideaki Yokoo; Yoshiki Arakawa; Junki Mizusawa; Noriko Mitome; Keita Sasaki; Haruhiko Fukuda; Yoshitaka Narita; Brain Tumor Study Group of the Japan Clinical Oncology Group

doi:10.1093/jjco/hyag090

PubMed · 42315131

A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART).

Kota Kawabata·Fumiharu Ohka·Ryuta Saito·Tsuyoshi Onoe·Hideyuki Harada·Takashi Sasayama·Hideaki Yokoo·Yoshiki Arakawa·Junki Mizusawa·Noriko Mitome·Keita Sasaki·Haruhiko Fukuda·Yoshitaka Narita·Brain Tumor Study Group of the Japan Clinical Oncology Group

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Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy. Patients refractory to high-dose methotrexate-based induction therapy have an extremely poor prognosis. Although whole-brain radiotherapy (WBRT) is the standard salvage treatment and provides potent tumor control, early functional deterioration and late neurocognitive toxicity remain major concerns. A phase I/II trial on relapsed or refractory PCNSL demonstrated favorable efficacy and tolerability of tirabrutinib, a second-generation selective Bruton's tyrosine kinase inhibitor. Tirabrutinib's oral administration has enabled outpatient management. However, its clinical value for induction-refractory PCNSL remains uncertain. We designed a multicenter, randomized phase II/III trial (JCOG2314) to assess the non-inferiority of tirabrutinib to WBRT in overall survival and its potential to reduce functional deterioration and cognitive impairment. A total of 94 patients from 49 institutions will be enrolled over 4 years. The trial has been registered in the Japan Registry of Clinical Trials (study number: jRCT1031250645).

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Humans Salvage Therapy Central Nervous System Neoplasms Lymphoma Female Cranial Irradiation Male Pyrimidines Protein Kinase Inhibitors HD-MTX-based induction therapy primary central nervous system lymphoma refractory PCNSL tirabrutinib whole-brain radiotherapy Journal Article Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Clinical Trial, Phase III

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Kota Kawabata, Fumiharu Ohka, Ryuta Saito, Tsuyoshi Onoe, Hideyuki Harada, Takashi Sasayama, Hideaki Yokoo, Yoshiki Arakawa, Junki Mizusawa, Noriko Mitome, Keita Sasaki, Haruhiko Fukuda, Yoshitaka Narita, Brain Tumor Study Group of the Japan Clinical Oncology Group. 2026-09-09. A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART).. https://doi.org/10.1093/jjco/hyag090

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