A Phase 2 Clinical Trial to Evaluate Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia

NCT05979948 | Unknown Phase 2

• 1 other identifier: CZ-WM01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy of zanubrutinib combined with BR (Bendamustine/Rituximab) regimen in Chinese participants with newly-diagnosed Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM). The investigators propose this combination will improve the deep remission compared to single Zanubrutinib or BR regimen and can be a time-limited regimen which will reduce the life-time therapy and benefit the patients.

Conditions

Waldenström's Macroglobulinemia

Keywords

Waldenström's macroglobulinemia; Zanubrutinib; BR regimen; newly-diagnosed

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response

  up to the end of 12 cycles of treatment(each cycle is 28 days)

• The best deep response rate

  defined as complete response (CR) and very good partial response (VGPR)

  Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  Up to 6 years post first dose

• Overall Survival (OS)

  Up to 6 years post first dose

• minimal residual disease (MRD) rate

  Up to 6 years post first dose

Study Arms (1)

zanubrutinib combined with BR regimen

EXPERIMENTAL

Drug: zanubrutinib,160 mg oral capsules twice daily for 12 months Drug: Bendamustine,70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles. Drug: Rituximab,375 mg/m2 intravenously on day 0 of each cycle for 6 cycles.

Drug: Zanubrutinib; Drug: Bendamustine; Drug: Rituximab

Interventions

Zanubrutinib DRUG

Zanubrutinib, 160 mg oral capsules twice daily for 12 months

zanubrutinib combined with BR regimen

Bendamustine DRUG

Bendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles.

zanubrutinib combined with BR regimen

Rituximab DRUG

Rituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles

zanubrutinib combined with BR regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be enrolled:
• Newly diagnosed patients with waldenström's macroglobulinemia meeting at least one criterion for treatment according to consensus panel criteria from the eleventh IWWM.
• ECOG score: 0-3 points, estimated survival time exceeding 3 months.
• Did not receive any treatment for Waldenström's macroglobulinemia before screening, except for glucocorticoid therapy for autoimmune hemolysis.
• No serious damage to main organs, and meet the following laboratory examination indicators: creatinine clearance rate≥40ml/min, total bilirubin≤1.5 times of the upper limit of normal range; AST and ALT≤2.5 times of the upper limit of normal range; Myocardial enzyme≤2 times of the upper limit of normal range; ECHO must demonstrate left ventricular ejection fraction (LVEF) within the normal range, and no ECG abnormality with clinical significance.
• Neutrophil count≥1.5×10\^9/L without growth factor therapy within 7 days before screening; Platelet count≥50×10\^9/L without growth factor support or transfusion within 7 days before screening; Hemoglobin≥60 g/L without erythropoietin (EPO) support or transfusion within within 7 days before screening.
• No history of paroxysmal atrial fibrillation or chronic persistent atrial fibrillation.
• Able to swallow and Oral administration.
• The subjects complete all screening and evaluations listed in all trial protocols.
• The subjects who signed the informed consent form for chemotherapy.

You may not qualify if:

• Waldenström's macroglobulinemia with amyloidosis or POEM syndrome
• HIV positive, or patients with active hepatitis A, hepatitis B, and hepatitis C infection; Or the number of copies of hepatitis B virus\>10\^2.
• Accompanied by other serious unstable diseases, including heart failure, renal failure, liver failure, hemorrhagic diseases, uncontrollable diabetes, etc.
• In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required.
• Serious infectious diseases (uncured pulmonary tuberculosis, pulmonary aspergillosis, etc.).
• Other uncontrolled malignancies (excluding non Melanoma skin cancer, cervical cancer in situ, bladder cancer cancer and breast cancer with disease-free survival of more than 5 years).
• Individuals with epilepsy, dementia, and other mental disorders who require medication treatment and are unable to understand or follow the research protocol.
• Drug use, medical, psychological, or social conditions that may interfere with participants' participation in the study or evaluation of the results.
• Pregnant and lactating women.
• Patients who are accounted to be not appropriate for this trail by investigator.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead
• RenJi Hospital: collaborator
• Huashan Hospital: collaborator
• Shanghai 6th People's Hospital: collaborator
• Huadong Hospital: collaborator

Study Sites (1)

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, 200020, China

RECRUITING

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

zanubrutinib; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Juan Du, Doctor

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haiyan He, Master

CONTACT

+8613661513012; doctorhehaiyan@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 30, 2023
• First Posted: August 7, 2023
• Study Start: August 1, 2023
• Primary Completion: April 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)