ClinicalTrials.gov record NCT07169565
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
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase I, open-label study tests a time-limited combination of ibrutinib followed by bendamustine plus rituximab in adults with Waldenström Macroglobulinemia who have been treated with ibrutinib. Part 1 uses a 3+3 dose‑de‑escalation of bendamustine to find the maximum tolerated and recommended Phase II dose; Part 2 expands at that dose to further assess safety and response. Treatment is given over a few fixed 28‑day cycles (ibrutinib daily with bendamustine and rituximab for three cycles, then one additional cycle of bendamustine+rituximab for those who meet response criteria) followed by follow-up.
What it is studying. The study is testing the safety and tolerability of a fixed-duration regimen of ibrutinib plus bendamustine and rituximab. It aims to identify the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of bendamustine when given with fixed-dose ibrutinib and rituximab, measure early treatment responses after the planned cycles, monitor for an IgM rebound after stopping therapy, and explore links between biomarkers (for example, CXCR4 mutation status) and clinical outcomes.
What the researchers hope to learn. Scientific goals: determine the MTD and RP2D of bendamustine in this combination; assess frequency and severity of treatment-emergent adverse events at that dose; estimate overall response rate after the planned cycles; measure duration of response and progression-free survival up to about 24 months; quantify IgM rebound within 2 months after stopping treatment; and explore biomarker correlations with outcomes.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
This is a two-part, non-randomized, open-label Phase I clinical study. The research consists of:
- 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;
- 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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Ibrutinib
- Bendamustine
- Rituximab
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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.
- 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).
- Patient has an estimated life expectancy ≥6 months.
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:
- ALT >3 × ULN
- AST >3 × ULN
- Total bilirubin (TBIL) >2 × ULN
- Serum creatinine clearance <30 mL/min.
- 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;
- New York Heart Association (NYHA) classification ≥ Class III;
- Left ventricular ejection fraction (LVEF) <50%;
- History within 6 months prior to enrollment: myocardial infarction, unstable angina, severe unstable ventricular arrhythmias, or any other arrhythmia requiring treatment; history of clinically significant pericardial disease; or ECG evidence of acute ischemia or active conduction system abnormalities.
- 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.
- Major surgery within 14 days prior to enrollment (excluding lymph node biopsy) or anticipated need for major surgery during the study.
- History or current diagnosis of another malignancy (except adequately controlled non-melanoma skin basal cell carcinoma, carcinoma in situ of the breast/cervix, and other malignancies effectively controlled without treatment for the past five years).
- Pregnant or lactating women, or women of childbearing potential not using contraception.
- Hypersensitivity to any of the study drugs or their components.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, gastrectomy, extensive small bowel resection potentially affecting absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restriction/bariatric surgery (e.g., gastric bypass).
- History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
- History of bleeding diathesis (e.g., hemophilia, von Willebrand disease).
- Requirement for or ongoing anticoagulation therapy with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days prior to the first dose of study drug.
- Diagnosis of gastrointestinal ulcer by endoscopy within 3 months prior to the first dose of study drug.
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants take oral ibrutinib daily and attend clinic for three 28‑day treatment cycles; they also receive IV rituximab once per cycle and IV bendamustine on Days 1–2 of each cycle (bendamustine infusions last about 60–120 minutes). Before and during treatment they will have frequent safety checks and blood tests (including IgM levels), disease assessments to measure response, and baseline and on-study biomarker samples. Cycle 1 includes close monitoring for dose‑limiting toxicities and dose reductions are possible per protocol. Patients who meet the response criteria receive one additional cycle of BR, then stop treatment and enter follow‑up monitoring (including checks for IgM rebound).
How the study is structured. Interventional, non-randomized, open-label Phase I study with a single treatment group. Part 1 uses a 3+3 dose‑de‑escalation of bendamustine (testing 70, 60, then 50 mg/m²) with fixed-dose ibrutinib (420 mg/day) and rituximab (375 mg/m²) over 28‑day cycles to find the MTD/RP2D. Part 2 enrolls additional patients at the chosen dose to further assess safety, side effects, and response rates.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- No sites are listed on the registry yet. Where will the study take place?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Sep 1, 2025 (estimated)
- Primary completion
- Sep 1, 2028 (estimated)
- Study completion
- Sep 1, 2028 (estimated)
- Target enrollment
- 21 participants (estimated)
- Last updated on registry
- Sep 11, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, China
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Shuhua Yi 📞 86-15900265415 ✉ yishuhua@ihcams.ac.cn
Participating sites
Study locations have not been posted on ClinicalTrials.gov yet. This study is not yet recruiting, so sites may be added when recruitment begins. The central study contact above may be able to tell you about planned sites.
Terms used on this page · explanations by MedicalUpdates.ai
- randomized
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- 3+3
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- Maximum Tolerated Dose
- The highest dose found in a dose-escalation study that can be given without too many dose-limiting side effects.
- Phase II
- A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
- RP2D
- The dose chosen at the end of a phase 1 study for testing in later studies, based on safety and other measurements.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Dose-Limiting Toxicity
- A side effect, defined in advance, that is severe enough to limit how far the dose can be raised in a dose-escalation study. How many such events stop escalation is set by the study's rules.
- VGPR
- A response category used in some blood conditions meaning the disease marker has fallen a great deal but not disappeared. The exact definition depends on the condition and the study.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- Primary Objective
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- biomarkers
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
- Complete Response
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
- Informed Consent Form
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- ECOG performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- prior treatment
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- Upper Limit of Normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- QTc
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- women of childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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