Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM

NCT06561347 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-294
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM). The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.

Conditions

Waldenstrom Macroglobulinemia

Keywords

MW; Untreated

Outcome Measures

Primary Outcomes (1)

• Very Good Partial Response (VGPR) or Better Response Rate

  Assessed using 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria. All participants will be gauged for very good partial response (VGPR) rate or better.

  Day 1 to 5 years post treatment

Secondary Outcomes (9)

• Treatment Related Adverse Events

  Day 1 to 5 years post treatment

• Overall Response Rate

  Day 1 to 5 years post treatment

• Major Response Rate

  Day 1 to 5 years post treatment

• Complete Response Rate

  Day 1 to 5 years post treatment

• Median Time to Response

  Day 1 to 5 years post treatment

Study Arms (1)

Zanubrutinib + Bendamustine + Rituximab

EXPERIMENTAL

Zanubrutinib will be taken orally once daily on days 1-28 of cycles 1-15. Bendamustine will be given by intravenous infusion over about 10 to 60 minutes on days 1 and 2 of cycles 1 to 4. Rituximab will be given by intravenous infusion over about 30 minutes on day 1 of cycles 1 to 4. Drug diaries will be provided to participants to document information about the study treatment being taken.

Drug: Zanubrutinib; Drug: Bendamustine; Drug: Rituximab

Interventions

Zanubrutinib DRUG

A potent, specific, and irreversible Bruton tyrosine kinase (BTK) inhibitor

Also known as: BGB-3111

Zanubrutinib + Bendamustine + Rituximab

Bendamustine DRUG

Alkylating agent

Zanubrutinib + Bendamustine + Rituximab

Rituximab DRUG

Monoclonal antibody

Zanubrutinib + Bendamustine + Rituximab

Eligibility Criteria

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

You may qualify if:

• Clinicopathological diagnosis of waldenström macroglobulinemia (WM) per the second international workshop on waldenström macroglobulinemia (IWWM2) criteria
• Presence of any MYD88 and CXCR4 mutation status, including MYD88 L265P mutation plus CXCR4 wild type, MYD88 L265P mutation plus CXCR4 mutation, or MYD88 wild type
• Meeting criteria for treatment per IWWM2 criteria. At least one of the following:
• Constitutional Symptoms (at least one of the following)
• Recurrent fever
• Night sweats
• Fatigue
• Weight loss
• Progressive or symptomatic lymphadenopathy or splenomegaly
• Hemoglobin ≤ 10 g/dL
• Platelet count ≤ 100 k/uL
• Hyperviscosity syndrome
• Symptomatic peripheral neuropathy
• Systemic amyloidosis
• Renal insufficiency

You may not qualify if:

• Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form
• Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed while enrolled in this study
• Participants with known CNS involvement by WM
• Participants with known history of Human Immunodeficiency Virus (HIV)
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (antiHBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded.
• Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded.
• Concurrent systemic immunosuppressant therapy. Systemic steroids at doses \<20mg prednisone per day are permitted.
• Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
• Concurrent administration of warfarin or warfarin derivatives.
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
• Major surgery within 4 weeks of first dose of study drug.
• History of severe bleeding disorder such as hemophilia A, hemophilia B, or history of spontaneous bleeding requiring blood transfusion or other medical intervention. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
• Participants with inability to swallow pills.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• BeiGene: collaborator

Study Sites (5)

Colorado Blood Cancer Institute (CBCI)

Denver, Colorado, 80218, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

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

• Andrew Branagan, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Branagan, MD, PhD

CONTACT

617-724-4000; abranagan@mgh.harvard.edu

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: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 20, 2024
• Study Start: December 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (5)