Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström M… (NCT07169565) | Clinical Trial Compass
Not Yet RecruitingPhase 1
Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia
21 participantsStarted 2025-09-01
Plain-language 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 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* Patients failing to achieve ≥MR are withdrawn.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.
Who can participate
Age range
18 Years – 75 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Patient fully understands the study, voluntarily participates, and signs the Informed Consent Form (ICF).
. Patient of any gender, aged ≥18 years and ≤75 years.
. Patient must meet diagnostic criteria for Waldenström Macroglobulinemia (WM) and be MYD88 L265P mutation positive.
. Patient has documented baseline IgM levels and disease assessment parameters (including liver, spleen, lymph nodes; if extramedullary lesions exist, include assessment of other extramedullary sites) prior to ibrutinib use, to facilitate subsequent efficacy evaluation.
. ECOG performance status score of 0-1.
. Patient has received ≥12 cycles of ibrutinib monotherapy, achieved a treatment response (but not Complete Response (CR) ), and is currently on a treatment plateau.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
. Patient has maintained good treatment tolerance (experienced no Grade ≥3 adverse reactions during ibrutinib therapy) and is still receiving ibrutinib.
. Patient has no prior treatment with Bendamustine combined with Rituximab (BR) regimen.
Exclusion criteria
. Diagnosis or treatment for a malignancy other than B-cell Non-Hodgkin Lymphoma (B-NHL) within the past year (including active Central Nervous System lymphoma). Received other anti-tumor therapies (including chemotherapy, targeted therapy, hormonal therapy, anti-tumor Chinese herbs with activity) within 4 weeks prior to study drug administration (excluding ibrutinib) or participated in other clinical trials receiving investigational drugs.
. Clinical evidence of transformation to large cell lymphoma.
. Non-lymphoma related liver or kidney impairment:
. Other severe medical conditions that could interfere with the study (e.g., uncontrolled diabetes, gastric ulcer, other severe cardiopulmonary diseases), as determined by the investigator.
. Cardiac function or disease meeting any of the following:
. Long QTc syndrome or QTc interval \>480 ms;
. Complete left bundle branch block, second- or third-degree atrioventricular block;
. Severe, uncontrolled arrhythmias requiring drug therapy;