A Phase 1 interventional study of Ibrutinib and Bendamustine in Waldenström Macroglobulinemia (WM), sponsored by Institute of Hematology & Blood Diseases Hospital, China. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-09-11.
Sponsored by Institute of Hematology & Blood Diseases Hospital, China · Phase 1, Interventional, and Treatment
This is a two-part, non-randomized, open-label Phase I clinical study. The research consists of:
Key Study Design Details:
Pre-enrollment \& Eligibility:
Treatment Regimen:
Fixed Doses:
Part I (3+3 Dose Escalation):
After 1 treatment cycle:
After 3 total cycles:
Part II (Dose Expansion):
Objectives:
Terminology Notes:
365 studies on the registry are indexed under Waldenstrom Macroglobulinemia; 62 are open to participants now.
This study's planned enrollment of 21 is below the median of 40 across 316 interventional studies indexed under Waldenstrom Macroglobulinemia.
Browse Waldenstrom Macroglobulinemia studies →Institute of Hematology & Blood Diseases Hospital, China is the lead sponsor of 398 studies on the registry; 293 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Laboratory values:
Exclusion Criteria
Non-lymphoma related liver or kidney impairment:
Cardiac function or disease meeting any of the following:
Known history of Human Immunodeficiency Virus (HIV) infection, or active Hepatitis B Virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
Note: Active HBV infection is defined as meeting ALL THREE criteria: a. HBV DNA quantification ≥2000 IU/mL; b. ALT ≥2 × ULN; c. Hepatitis not attributable to other causes (e.g., disease itself, drugs). Patients initially diagnosed with active HBV infection who convert to inactive HBV status after anti-HBV therapy may be enrolled provided they receive adequate anti-HBV prophylaxis.
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.
Drug: Ibrutinib · Drug: Bendamustine · Drug: Rituximab
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).
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.
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.
Phase 1: Dose Escalation (Part 1) Incidence of Dose-Limiting Toxicities (DLTs)
Proportion of participants experiencing protocol-defined DLTs during Cycle 1 (28 days). DLTs include Grade ≥3 non-hematologic or specific hematologic toxicities (e.g., febrile neutropenia, Grade 4 thrombocytopenia \>7 days) attributed to IBR regimen per NCI CTCAE v4.0 criteria (Section 2.4).
Time frame: Cycle 1 (Days 1-28)
Phase 1: Dose Escalation (Part 1) Maximum Tolerated Dose (MTD) of Bendamustine
Highest dose level (70/60/50 mg/m²) at which ≤1 of 6 participants experience DLTs during Cycle 1, determined via 3+3 dose-escalation design (Section 2.1).
Time frame: End of Dose Escalation Phase (approximately 6 months)
Phase 1: Dose Escalation (Part 1) Recommended Phase 2 Dose (RP2D)
Optimal dose of Bendamustine for expansion phase, derived from MTD evaluation integrated with safety/tolerability data (Section 2.1).
Time frame: End of Dose Escalation Phase (approximately 6 months)
Phase 2: Dose Expansion (Part 2) Treatment-Emergent Adverse Events (TEAEs) at RP2D
Frequency and severity of TEAEs (Grade ≥3 per NCI CTCAE v4.0) attributed to IBR regimen at the RP2D. Includes hematologic, non-hematologic, and serious adverse events.
Time frame: From first dose until 30 days after last dose (up to 5 months)
Phase 2: Dose Expansion (Part 2) Overall Response Rate (ORR) at RP2D
Proportion of participants achieving ≥Partial Response (PR) per Consensus Panel Criteria from the 8th International Workshop on Waldenström Macroglobulinemia (IWWM-8) after 3 cycles of IBR therapy.
Time frame: At end of Cycle 3 (Day 84 ±3 days)
IgM rebound rate
Proportion of participants experiencing an IgM rebound, defined as a ≥25% increase in serum IgM levels from the end-of-treatment measurement, within 2 months after discontinuation of the time-limited therapy.
Time frame: At 2 months after the last dose of study treatment
Duration of Response (DOR)
Time from the date of initial documented response (partial response or better) to the date of documented disease progression or death from any cause, whichever occurs first.
Time frame: From the first documented response until disease progression/recurrence (assessed up to 24 months)
Progression-Free Survival (PFS)
Time from the first dose of study drug to the date of documented disease progression or death from any cause, whichever occurs first.
Time frame: From first dose until disease progression or death (assessed up to 24 months)
Biomarker correlation with efficacy
Assessment of the association between specific biomarker levels (e.g., CXCR4 mutation status) and clinical efficacy outcomes (e.g., overall response rate).
Time frame: Biomarker samples collected at baseline; efficacy assessed through study completion (approximately 24 months)
Correlation of Baseline Biomarker Status with Treatment Efficacy
To assess the association between the presence of specific somatic mutations (e.g., MYD88, CXCR4) detected at baseline and the achievement of a clinical response (Partial Response or better as defined by IWWM-8 criteria) following combination therapy. The strength of the association will be measured using odds ratios from logistic regression analysis.
Time frame: Biomarker status: At screening (Day -28 to Day 1); Efficacy assessment: At the end of Cycle 3 (Day 84)
Biomarker Correlation with Adverse Reactions
To assess the impact of specific biomarkers (e.g., pharmacogenetic variants) on the incidence and severity of treatment-emergent adverse events (e.g., neutropenia, rash) after combination therapy. The association will be analyzed using appropriate statistical tests.
Time frame: Biomarker samples collected at baseline (Day 1 Cycle 1); safety assessed from first dose until 30 days after last dose (approximately 24 months)
Temporal Changes in Biomarker Burden
Quantitative changes in mutation burden (e.g., MYD88 L265P variant allele frequency) from baseline to end of Cycle 3, measured by ddPCR in bone marrow/peripheral blood samples.
Time frame: Baseline (screening) vs. End of Cycle 3 (Day 84 ±3 days)
Impact of Germline Genetic Variants on Incidence of Specific Adverse Reactions
To evaluate the relationship between predefined germline pharmacogenetic variants (e.g., in genes encoding CYP metabolizing enzymes) and the occurrence of specific Grade ≥3 adverse events (e.g., neutropenia, rash) attributed to the study regimen. The analysis will report hazard ratios from a Cox proportional-hazards model.
Time frame: Genetic variant status: At screening (Day -28 to Day 1); Safety assessment: From first dose until 30 days after last dose (up to 24 weeks) Summary of Revisions:
No study locations are listed for this record.
Plan to share: No — The data collected in this study are sensitive patient information. Due to privacy restrictions outlined in the informed consent form and institutional policies, the individual participant data will not be made publicly available.
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.
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Waldenstrom Macroglobulinemia→
Institute of Hematology & Blood Diseases Hospital, China