Waldenström Macroglobulinemia (WM)

BTK inhibitors and BCL-2 inhibitors have demonstrated significant clinical activity in mature B-cell malignancies, and combination therapy may provide improved clinical benefit. This is a multi-center, open-label, single-arm Phase Ib/II clinical study. The purpose of this clinical trial is to investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of Rocbrutinib, a fourth-generation Bruton tyrosine kinase inhibitor (BTKi), in combination with the BCL-2 inhibitor Lacutoclax in patients with mature B-cell malignancies. The Phase Ib will use a classic 3+3 dose-escalation design to evaluate dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD), and identify the recommended dosing regimen. The Phase II portion is intended to further evaluate the efficacy and safety of the combination therapy.

This study is designed to characterize the safety, tolerability, and anti-tumor activity of MDX2003 in patients with different types of lymphoma

This study is a prospective phase II clinical trial designed to evaluate the deep response rate of the ZBR regimen (zanubrutinib combined with reduced-dose bendamustine and CD20 Monoclonal Antibody ) in treatment-naïve symptomatic Waldenström macroglobulinemia (WM) patients. Eligible patients will receive four cycles of the ZBR regimen, followed by zanubrutinib monotherapy for an additional eight months. The assessment period spans from the initiation of treatment until 12 months after treatment completion, with efficacy evaluations conducted every three cycles. Patients will be withdrawn from the study if they experience disease progression (PD) or show no response to treatment. Minimal residual disease (MRD) assessments will be performed at the end of the 3rd and 6th treatment cycles, as well as 12 months after treatment completion, involving evaluations of both bone marrow and peripheral blood MRD rates

This is a two-part, non-randomized, open-label Phase I clinical study. The research consists of: 1. A 3+3 dose-escalation phase to determine the Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of the I+BR regimen in Waldenström Macroglobulinemia (WM) patients; 2. A dose-expansion phase to evaluate the safety, tolerability, and efficacy of the time-limited regimen at the MTD/RP2D. Key Study Design Details: Pre-enrollment \& Eligibility: * Patients undergo efficacy and tolerability assessment before enrollment. * Eligible patients receive I+BR therapy. Treatment Regimen: * Bendamustine: Tested at three dose levels (70 mg/m², 60 mg/m², and 50 mg/m²) based on prior IBR data in B-cell lymphomas. A 3+3 dose de-escalation design is employed. * Fixed Doses: * Ibrutinib: 420 mg/day * Rituximab: 375 mg/m² Part I (3+3 Dose Escalation): * Start with 3 patients receiving bendamustine 70 mg/m². * After 1 treatment cycle: * Assess Dose-Limiting Toxicity (DLT) (DLT criteria defined separately). * Patients without DLT proceed to 2 additional cycles of IBR. * After 3 total cycles: * Efficacy assessment is performed. * Patients achieving minimal response (MR) or better (i.e., MR, PR, VGPR, CR) receive 1 cycle of BR, then cease treatment and enter follow-up. * Patients failing to achieve ≥MR are withdrawn. * Primary Objective: Evaluate safety and identify MTD. Part II (Dose Expansion): * Enroll 15 additional patients at MTD/RP2D. * Objectives: * Further assess safety and efficacy; * Monitor IgM rebound within 2 months after completing therapy (3 cycles I+BR → 1 cycle BR); * Explore correlations between biomarkers and clinical outcomes. Terminology Notes: * I+BR: Ibrutinib + Bendamustine/Rituximab * DLT: Dose-Limiting Toxicity * MTD: Maximum Tolerated Dose * RP2D: Recommended Phase II Dose * Efficacy thresholds: MR (Minimal Response), PR (Partial Response), VGPR (Very Good Partial Response), CR (Complete Response) * Time-limited therapy: Fixed-duration treatment designed to avoid indefinite dosing.