Efficacy and Safety of Brentuximab Vedotin Combined With Lisaftoclax in CD30+ Cutaneous T-cell Lymphoma (CTCL)

This is a prospective, single-center, open-label, randomized, controlled phase II clinical trial. The main purpose of this study is to evaluate the efficacy and safety of combining brentuximab vedotin (an anti-CD30 antibody-drug conjugate, ADC) with lisaftoclax (APG-2575, a novel B-cell lymphoma 2 (BCL-2) inhibitor) in patients with CD30-positive cutaneous T-cell lymphoma (CTCL), specifically including mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Previous studies suggest that the overexpression of the anti-apoptotic protein BCL-2 may contribute to brentuximab vedotin resistance in CTCL. Researchers hypothesize that adding a highly selective BCL-2 inhibitor (lisaftoclax) can reverse this drug resistance, enhance tumor cell apoptosis, and improve clinical outcomes. In this study, approximately 46 eligible patients will be randomly assigned in a 1:1 ratio to one of two treatment arms: Monotherapy arm (control): Patients will receive brentuximab vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles. Combination arm (experimental): Patients will receive the same brentuximab vedotin regimen. Additionally, starting from the 6th cycle, patients will receive oral lisaftoclax. To mitigate the risk of tumor lysis syndrome (TLS), a daily dose ramp-up will be implemented in the first cycle of lisaftoclax. Subsequently, lisaftoclax will be administered at a targeted dose of 600 mg daily on days 1 to 10 of each 21-day cycle, for a total of 9 combination cycles. The primary endpoint of the study is the objective response rate (ORR) evaluated at the end of the 16 cycles. Secondary endpoints include the improvement of skin lesions (evaluated by modified severity-weighted assessment tool (mSWAT) score), pruritus relief (visual analog scale (VAS) score), and the incidence of adverse events (AEs). Independent, blinded assessors will be utilized to evaluate the clinical responses to reduce bias.