Status:
NOT_YET_RECRUITING
Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia
Lead Sponsor:
Institute of Hematology & Blood Diseases Hospital, China
Conditions:
Waldenström Macroglobulinemia (WM)
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
Brief 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 ...
Eligibility Criteria
Inclusion
- 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.
Exclusion
Key Trial Info
Start Date :
September 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2028
Estimated Enrollment :
21 Patients enrolled
Trial Details
Trial ID
NCT07169565
Start Date
September 1 2025
End Date
September 1 2028
Last Update
September 11 2025
Active Locations (0)
Enter a location and click search to find clinical trials sorted by distance.
No Results Found
We couldn’t find results for the location/zipcode entered or within the selected range. Please check your input or adjust your search.