Five patients that responded to therapy had the best response 6?months after the final treatment with rituximab. Seven patients were enrolled. The best overall response rate according to the 1996 NCI-WG Guidelines, the primary endpoint of the study, was 71.4% (95% confidence interval, 29.0C96.3%), with one patient achieving complete response. No deaths or progression occurred during follow-up. The main adverse event was hematotoxicity. CD4-positive T-cell count decreased in all patients; most patients showed 3-Methyluridine no reduction in serum immunoglobulin G. Conclusion Although the number of patients was limited, FCR appears to be effective with manageable toxicity for treatment-na?ve fit Japanese patients with CD20-positive CLL. Clinical trial number JapicCTI-132285. strong class=”kwd-title” Keywords: rituximab, chronic lymphocytic leukemia, phase II clinical trial, FCR Introduction Chronic lymphocytic leukemia (CLL) is a rare subtype of leukemia in Japan, accounting for 1C2% of all Japanese lymphoid neoplasm cases (1). In patients with CLL, treatment is typically initiated when the patient has evidence of active disease (2) and initial treatment is selected based on the comorbidity (fitness) 3-Methyluridine and/or chronological age of patients (2). The combination of fludarabine, cyclophosphamide and rituximab (FCR) has been the standard treatment option for previously untreated patients with CLL who are young and fit. In the CLL8 study, a pivotal phase III trial, the German CLL Study Group compared FCR to combination therapy with fludarabine and cyclophosphamide (FC) in treatment-na?ve CLL patients who were scored up to 6 on the Cumulative Illness Rating Scale (CIRS) and who had creatinine clearance 70?ml/min. The results showed extension of progression-free survival (PFS; median duration: 51.8?months [95% confidence interval (CI), 46.2C57.6] vs. 32.8?months [95% CI, 29.6C36.0], em P /em ? ?0.0001) (3) in the FCR arm with an improved response rate (90 vs. 80%, em P /em ? ?0.0001) and complete response (CR) rate (44 vs. 22%, em P /em ? ?0.001). Notably, overall survival was significantly longer in the FCR arm (median duration: not reached vs. 86.0?months, em P /em ?=?0.001) (4). Additionally, in long-term follow-up for a phase 2 study of the FCR regimen at MD Anderson Cancer Center, about half of patients with a mutated immunoglobulin heavy chain variable gene achieved PFS at 12.8?years and a plateau was seen on the PFS curve (5). However, FCR has not been utilized in Japan because rituximab for CLL has not yet been approved there. We thus conducted a clinical study to confirm the 3-Methyluridine efficacy and safety of rituximab in Japanese patients with untreated CLL in accordance with the study design for the CLL8 study. Patients and methods Study design and patients This study was a prospective, open-label, single-arm, multicenter phase II trial, based on the study design for the CLL8 trial Rabbit Polyclonal to VEGFR1 (phospho-Tyr1048) (3), and was conducted at six institutions in Japan. As in the CLL8 trial, patients received FCR therapy every 28?days for up to six cycles (rituximab 375?mg/m2 on Day 1 of Cycle 1 and 500?mg/m2 on Day 1 of Cycles 2C6; fludarabine 25?mg/m2/day and cyclophosphamide 250?mg/m2/day for the first 3?days of each cycle). Before each cycle of rituximab infusion, patients were premedicated with 50C100?mg oral diphenhydramine hydrochloride, 1000?mg oral acetaminophen and 100?mg intravenous prednisolone. Before Cycle 1, 0.2?mg/kg/day rasburicase was administered to prevent tumor lysis syndrome. From Cycle 2 onward, administration of an antihyperuricemic was recommended. Response to treatment was assessed at the completion of Cycle 3 and 1, 3 and 6?months after final rituximab administration, in accordance with the response criteria stipulated in the 1996 NCI-WG Guidelines (6). Response rates were calculated based on the best response data. After completion of Cycle 3, further treatment was continued at the discretion of the investigator in patients who had achieved a CR or partial response (PR) assessment and in those with stable disease (SD). The patients were followed for up to 1?year after initial rituximab administration. In the protocol, feasibility was evaluated by the rate of grade 3 adverse events or adverse drug reactions. Adverse events and adverse drug reactions were coded using the Japanese version of the ICH Medical Dictionary for Regulatory Activities (MedDRA/J) and were then tabulated by preferred terms. Adverse event severity was assessed in accordance with the.