Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenstrm Macroglobulinemia

• Status: NOT_YET_RECRUITING
• Trial end date: 2028-09-01

Summary

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 Waldenstrm 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/m, 60 mg/m, and 50 mg/m) 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/m

Part I (3+3 Dose Escalation):

• Start with 3 patients receiving bendamustine 70 mg/m.
• 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• Patients failing to achieve MR are withdrawn.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.

• Phase: PHASE1

Details

• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Treatments: Bendamustine Hydrochloride; ibrutinib; Rituximab