RCLARITY: A Prospective Phase II Study of Rituximab Combined With Lenalidomide and Chidamide (RLC) for the Treatment of Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma.

Relapsed/refractory (r/r) angioimmunoblastic T-cell lymphoma (AITL) is associated with a dismal prognosis, with historical overall survival (OS) < 6 months, underscoring the urgent need for novel therapies. We conducted the RCLARITY trial to evaluate the efficacy and safety of a chemotherapy-free regimen in this patient population. This single-arm, multicenter, prospective Phase II trial enrolled adult patients with r/r AITL. Patients received rituximab (375 mg/m2 intravenously on Day 1), lenalidomide (15 mg orally on Days 1-21), and chidamide (30 mg orally twice weekly) in 28-day cycles for up to 6 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the overall response rate (ORR), OS, duration of response (DoR), and safety. In total, 28 patients were enrolled between August 2019 and June 2024. The median age was 64 years (range, 44-70), and 71.4% had refractory disease. The ORR was 71.4% (complete remission: 32.1%), median PFS was 5.5 months (95% confidence interval [CI], 3.5-7.6), median OS was 17.6 months (95% CI, 10.3-24.8), and median DoR among responders was 10.7 months (95% CI, 2.7-16.0). Notably, 50% of patients with clonal Ig heavy- or light-chain rearrangements achieved PFS > 16 months. All nine patients with baseline serum EBV-DNA positivity converted to undetectable levels after two cycles. No Grade 5 adverse events or venous thromboembolic events occurred. The most common hematological adverse events per cycle were leukopenia (14.3%), thrombocytopenia (12.4%), and neutropenia (11.4%). Overall, the RLC regimen induced clinically meaningful anti-tumor activity with manageable toxicity in patients with r/r AITL. Trial Registration: ClinicalTrials.gov identifier: NCT04319601.