Background: Forodesine, a potent purine nucleoside phosphorylase inhibitor, induces apoptosis mainly in T cells. Forodesine at relatively low dose was feasible but the response rate was not sufficient in early trials for PTCL and cutaneous T-cell lymphomas. A pivotal single-arm phase 1/2 study of forodesine at relatively high dose was conducted in patients with relapsed PTCL. Methods: Eligible patients, who had relapsed PTCL, confirmed by central pathology review according to the WHO classification 2008, and without major organ dysfunction, received forodesine 300 mg twice a day (BID) continuously. Tumor response was assessed with CT and PET by independent imaging review using IWC 2007 criteria. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: In the phase 1 part (n = 4), no DLTs were observed at 300 mg BID, determined as the recommended phase 2 dose. In the phase 2 part, 44 patients (median age 69; median number of previous treatment 2, range 1-9) received forodesine. The ORR in 41 evaluable patients was 22% (9 of 41; 90% CI 12.0-35.3) including 4 CR (10%) and 5 PR (12%), the lower limit of the 90% CI exceeded 10% threshold. Median PFS and OS were 2.0 and 14.5 months, respectively. The median time to response in 9 responders was 1.9 months (range 1.8-5.5) with median response duration not reached. The most common adverse events (AEs) ( ≥ G3) were lymphopenia (96%), leukopenia (42%), neutropenia (33%), thrombocytopenia (25%), and anemia (20%). Four patients (3 AITLs and 1 PTCL-NOS) developed secondary B-cell non-Hodgkin lymphomas (B-NHL), and one of them died of B-NHL and PD. Two patients developed peripheral neuropathy/myopathy of G3. At the point of data cut-off, among 44 subjects, treatment was discontinued in 37 [PD 30 (81%), AEs 4 (11%), and others 3 (8%)]. Conclusions: Forodesine at 300 mg BID appears to show better efficacy than that in the lower dose previous trial for relapsedPTCL despite some infections and secondary lymphomas possibly associated with lymphopenia. Forodesine would contribute as one of the reasonable options for the treatment of relapsed PTCL. Clinical trial information: NCT01776411