Combining Zanubrutinib with Bendamustine and Rituximab for Newly Diagnosed Waldenstrom Macroglobulinemia

Phase II Clinical Study of Zanubrutinib Combined With Bendamustine and Rituximab (ZBR) for Time-limited Treatment of Waldenstrom Macroglobulinemia

This study is testing a new treatment plan that combines Zanubrutinib with bendamustine and rituximab to see if it helps people with newly diagnosed Waldenstrom macroglobulinemia feel better and stay in remission longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine, rituximab, Zanubrutinib
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT05914662 on ClinicalTrials.gov

What this trial studies

This study evaluates the long-term effectiveness of a combination therapy using the BTK inhibitor Zanubrutinib along with bendamustine and rituximab for treating newly diagnosed symptomatic Waldenstrom macroglobulinemia. The approach aims to enhance remission depth, prolong remission duration, and improve both progression-free and overall survival rates. Participants will undergo six cycles of the combination therapy followed by six months of Zanubrutinib monotherapy. The study is designed to address the challenges of long-term treatment adherence and potential drug resistance associated with BTK inhibitors.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who have newly diagnosed symptomatic Waldenstrom macroglobulinemia and have not received prior treatment.

Not a fit: Patients who have previously undergone specific chemotherapy regimens or those with advanced disease not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival outcomes and quality of life for patients with Waldenstrom macroglobulinemia.

How similar studies have performed: While the combination of BTK inhibitors with other therapies has shown promise in related conditions, this specific approach is novel and has not been extensively tested in this patient population.

Eligibility criteria

Inclusion Criteria:

* The gender of the patient is not limited, and the age is ≥18 years old;
* Must meet WM's diagnostic standards;
* The patient is an untreated or patient who has not undergone standard treatment.
* The specific conditions are as follows:

  1. No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP
  2. No treatment regimen containing fludarabine
  3. Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids)
  4. The above treatment did not reach the treatment response (MR)
  5. If the above treatment has been applied, the treatment needs to be stopped for 2 weeks before entering the group to start treatment
* The indications for the treatment of indolent lymphoma mainly include (at least one of the following conditions):

  1. Symptomatic hyperviscosity;
  2. Symptomatic peripheral neuropathy;
  3. Amyloidosis;
  4. Cold agglutinin disease; cryoglobulinemia;
  5. Disease-related cytopenia (Hb\<100 g/L, PLT\<100×10\^9/L);
  6. Giant lymph nodes;
  7. Those with systemic systemic symptoms: for two weeks/recurrent fever (above 38℃) and not caused by infection, or Night sweats and/or weight loss \>10% within 6 months;
  8. The disease progresses rapidly, for example, the lymph nodes increase by more than 50% within 2 months, and/or peripheral blood lymphocytes absolute value doubling time \<6 months, and/or rapid hemoglobin or platelet non-autoimmune causes slow down
  9. When there is evidence that the disease has transformed.
* ECOG score ≤ 2 points
* Laboratory examination: neutrophils ≥ 0.75×10\^9/L; platelets ≥ 50×10\^9/L; total bilirubin ≤ 2.5 times upper limit; alanine aminotransferase/aspartate aminotransferase ≤3 times upper limit. Creatinine clearance rate ≥ 30ml/min.
* The patient's expected survival time is ≥ 3 months.

Exclusion Criteria:

* Malignant tumors (including active central nervous system lymphoma) other than B-NHL have been diagnosed or treated within the past year;
* There is clinical evidence that large cell lymphoma transformation has occurred;
* Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)\> 3 times the upper limit of normal value, aspartate aminotransferase (AST)\> 3 times the upper limit of normal value, total bilirubin (TBIL)\> upper limit of normal value 2 Times, serum creatinine clearance rate \<30ml/min;
* Other serious medical conditions will affect the study (such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). The decision-making power belongs to the researcher;
* Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
* Central nervous system dysfunction with clinical manifestations or central invasion (Bing-Neel syndrome);
* Patients who have undergone major surgery (not including lymph node biopsy) within the past 14 days or expected major surgery during treatment;
* Inability to swallow capsules or suffer from malabsorption syndrome, diseases that significantly affect gastrointestinal function, have undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, partial or complete intestinal obstruction.
* Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.
* Women who are pregnant or breastfeeding, women of childbearing age who have not taken contraception;
* Allergy to the drugs used.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Shuhua Yi, Dr. — Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
• Study coordinator: Shuhua Yi, Dr.

Conditions Waldenstrom Macroglobulinemia; Waldenstrom macroglobulinemia; Zanubrutinib; newly diagnosed