NCT07169565|Not Yet RecruitingPhase 1

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

Phase I Clinical Study of Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia

Institute of Hematology & Blood Diseases Hospital, China ClinicalTrials.gov

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Other study identifiers

Sponsor study identifier

IIT2022026

Study Type

interventional

Estimated enrollment

Locations

0 countries

Sites

N/A

Timeline

Study Start

September 1, 2025

Estimated (date passed)

This estimate has passed. The registry has not confirmed an actual date for this milestone.

Primary Completion

September 1, 2028

Estimated

Planned date reported by the registry; this milestone is not confirmed as achieved.

Study Completion

September 1, 2028

Estimated

Planned date reported by the registry; this milestone is not confirmed as achieved.

Brief Summary

This is a two-part, non-randomized, open-label Phase I clinical study. The research consists of:

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Patients failing to achieve ≥MR are withdrawn.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.

Registry Overview

Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.

Recruitment status: not yet recruiting
Estimated enrollment: 21 participants
Study completion date: September 1, 2028
Estimated
Planned date reported by the registry; this milestone is not confirmed as achieved.
Listed locations: 0 countries · 0 sites

Trial Relationships

Click on a node to explore related trials.

Some registry-reported names shown below are not yet linked in this graph.

Study Timeline

Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.

First Submitted
July 31, 2025
Actual (reported)
Study Start
September 1, 2025
Estimated (date passed)
This estimate has passed. The registry has not confirmed an actual date for this milestone.
First Posted
September 11, 2025
Actual (reported)
Primary Completion
September 1, 2028
Estimated
Planned date reported by the registry; this milestone is not confirmed as achieved.
Study Completion
September 1, 2028
Estimated
Planned date reported by the registry; this milestone is not confirmed as achieved.

Last Updated: September 11, 2025
Status Verified: September 2025
Last Update Submitted: September 5, 2025

Conditions

Waldenström Macroglobulinemia (WM)

Keywords

Waldenström Macroglobulinemiaibrutinibfixed dose

Outcome Measures

Primary Outcomes (5)

Interventions

IbrutinibDrug

Oral Bruton's tyrosine kinase (BTK) inhibitor administered at a fixed dose of 420 mg once daily. Capsules must be swallowed whole with water; do not open, break, or chew. If a dose is missed by ≤6 hours, take immediately; if \>6 hours, skip the dose and resume normal schedule the next day. Avoid grapefruit and Seville oranges (moderate CYP3A inhibitors). Treatment duration: 3 cycles (28 days/cycle) or until disease progression/unacceptable toxicity. Dose reduction is mandated for specific toxicities: 420 mg → 280 mg → 140 mg → discontinuation (per protocol-specified criteria). Use with caution in hepatic impairment (Child-Pugh A: reduce to 80 mg/day; Child-Pugh B/C: contraindicated).

Ibrutinib + BR Combination Therapy

BendamustineDrug

Intravenous alkylating agent dosed via a 3+3 dose de-escalation design (70 mg/m² → 60 mg/m² → 50 mg/m²). Infused over 60-120 minutes on Days 1-2 of each 28-day cycle for 3 cycles. Starting dose: 70 mg/m² (Dose Level 1); dose reduction triggered by Dose-Limiting Toxicity (DLT) events per protocol. In the dose-expansion phase, all subjects receive the MTD/RP2D established in Part 1. Concomitant live vaccines are prohibited. Dose delays (≤4 weeks) and reductions are required for Grade ≥3 hematologic/non-hematologic toxicities.

Ibrutinib + BR Combination Therapy

RituximabDrug

Intravenous anti-CD20 monoclonal antibody administered at a fixed dose of 375 mg/m² on Day 0 of each 28-day cycle for 3 cycles. Initial infusion starts at 50 mg/hour; if tolerated, increase by 50 mg/hour every 30 minutes (maximum: 400 mg/hour). Subsequent infusions start at 100 mg/hour with the same escalation. Premedication with acetaminophen and an antihistamine is required prior to each infusion. Permanently discontinue for Grade 4 infusion-related reactions or severe/life-threatening toxicity.

Ibrutinib + BR Combination Therapy

Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.

Eligibility Criteria

Age18 Years - 75 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.
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.
Laboratory values:
Neutrophils ≥1.0 × 10⁹/L
Platelets ≥50 × 10⁹/L
Hemoglobin ≥70 g/L
Total bilirubin ≤2 × Upper Limit of Normal (ULN)
Alanine aminotransferase (ALT) / Aspartate aminotransferase (AST) ≤3 × ULN
Creatinine clearance (CrCl) ≥30 mL/min (calculated by Cockcroft-Gault formula).
+1 more criteria

You may not qualify if:

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:
ALT \>3 × ULN
AST \>3 × ULN

Contact the study team to confirm eligibility.

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

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

First Submitted

Study Start

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (5)

Secondary Outcomes (4)

Other Outcomes (4)

Study Arms (1)

Ibrutinib + BR Combination Therapy

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Central Study Contacts

Study Design

Study Record Dates

Data Sharing

Source record

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

Study Start

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (5)

Secondary Outcomes (4)

Other Outcomes (4)

Study Arms (1)

Ibrutinib + BR Combination Therapy

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Central Study Contacts

Study Design

Study Record Dates

Data Sharing

Source record