Rituximab and Zanubrutinib in Patients With Indolent B-cell Lymphomas

NCT06350318 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-22005
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to establish the safety and efficacy of zanubrutinib in combination with rituximab for people with untreated B-cell lymphomas (marginal zone lymphoma and follicular lymphomas).

Conditions

Follicular Lymphoma; Marginal Zone Lymphoma; B-Cell Lymphoma

Keywords

B-Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate: Cohort A

  Overall response rate will be determined using a 5 point scale per the Lugano criteria.

  Up to 6 Months

• Overall Response Rate: Cohort B

  Overall response rate will be determined using a 5 point scale per the Lugano criteria.

  Up to 6 Months

Secondary Outcomes (2)

• Efficacy of Zanubrutinib and Rituximab

  Up to 24 months

• Safety and tolerability of combination Zanubrutinib and Rituximab

  Up to 24 Months

Study Arms (2)

Cohort A: Untreated Marginal Zone Lymphoma

EXPERIMENTAL

Rituximab (Standard of Care) will be administered for up to 6 cycles (28-day cycles). Cycle 1: Days 1, 8, 15, and 22. Cycle 2-6: Day 1, every 28 days. Rituximab: Intravenous rituximab formulations (IV rituximab or IV rituximab biosimilars will be administered by IV infusion at a dose of 375 mg/m2 per local institutional guidelines) or subcutaneous rituximab formulations (RITUXAN HYCELA) 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose per local institutional guidelines. Zanubrutinib 320 mg will be administered orally once daily starting on day 1 of cycle 1. Zanubrutinib will be continued once daily for up to 24 cycles or until disease progression or unacceptable toxicity occurs.

Drug: Zanubrutinib; Drug: Rituximab

Cohort B: Untreated Follicular Lymphoma

EXPERIMENTAL

Rituximab (Standard of Care) will be administered for up to 6 cycles (28-day cycles). Cycle 1: Days 1, 8, 15, and 22. Cycle 2-6: Day 1, every 28 days. Rituximab: Intravenous rituximab formulations (IV rituximab or IV rituximab biosimilars will be administered by IV infusion at a dose of 375 mg/m2 per local institutional guidelines) or subcutaneous rituximab formulations (RITUXAN HYCELA) 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose per local institutional guidelines. Zanubrutinib 320 mg will be administered orally once daily starting on day 1 of cycle 1. Zanubrutinib will be continued once daily for up to 24 cycles or until disease progression or unacceptable toxicity occurs.

Drug: Zanubrutinib; Drug: Rituximab

Interventions

Zanubrutinib DRUG

Zanubrutinib is an anti-cancer medication administered orally.

Also known as: Brukinsa

Cohort A: Untreated Marginal Zone Lymphoma; Cohort B: Untreated Follicular Lymphoma

Rituximab DRUG

Rituximab is a biologic medication administered intravenously or subcutaneously.

Also known as: Rituxin

Cohort A: Untreated Marginal Zone Lymphoma; Cohort B: Untreated Follicular Lymphoma

Eligibility Criteria

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

You may qualify if:

• Cohort A: Previously untreated MZL. Prior therapy with H. Pylori antibiotic therapy or hepatitis C antiviral therapy are allowed on Cohort A.
• Cohort B: Previously untreated FL
• Pathological confirmation of lymphoma: availability of archival tissue confirming diagnosis of MZL (cohort A) or FL (cohort B). Availability of formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens from within past 18 months from screening and pathological diagnosis confirmed by a pathologist at the participating site or willingness of the participant to undergo a fresh tumor biopsy if adequate archival tissue not available is required. This includes:
• MZL (Cohort A):
• Nodal MZL requiring systemic therapy
• Splenic MZL requiring systemic therapy
• Extra-nodal marginal zone lymphoma:
• Non-gastric/non-cutaneous MZL requiring systemic therapy.
• Cutaneous MZL will be eligible only if they have pathologically confirmed extra-cutaneous disease.
• Gastric MZL only if advanced stage disease requiring systemic therapy (e.g., stage IIE, II2, IV- supradiaphragmatic nodal or disseminated extranodal disease such as bone marrow or additional extra nodal sites.
• FL (Cohort B):
• a. Pathological grade 1, 2, or 3a based on the World Health Organization (WHO 2008) classification of tumors of hematopoietic and lymphoid tissue.
• \. Please note, grade 3B are excluded.
• All participants must have disease requiring systemic therapy rather than local radiation (ie, stage II only if not eligible for radiation therapy or with stage III/IV).
• All participants should have measurable disease. Measurable disease is defined as a lymph node or tumor mass that is ≥ 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT.

You may not qualify if:

• Prior therapy for lymphoma including chemotherapy or immunotherapy. Participant may have received corticosteroids but should be off them 5 days prior to study entry.
• Prior exposure to a BTK inhibitor.
• Known prior significant hypersensitivity to rituximab (not including infusion reactions).
• Prior history of malignancies unless the patient has been disease free for ≥ 2 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin; carcinoma in situ of cervix; carcinoma in situ of breast, localized prostate cancer, or superficial bladder cancer that has undergone curative therapy.
• Participants with evidence of large B cell transformation or other aggressive histology (such as large cells seen on biopsy or high PET avidity in a single node seen on PET scan) are not eligible.
• Known central nervous system (CNS) involvement by lymphoma.
• Known bleeding disorders (e.g., von Willebrand's disease or hemophilia).
• Concomitant use of warfarin or other Vitamin K antagonists.
• Requires ongoing treatment with a moderate or strongCYP3A inhibitor or inducer.
• Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1.
• Known infection with human immunodeficiency virus (HIV).
• Viral Hepatitis:
• Participants with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of detectable serum hepatitis B DNA viremia are not eligible for this study.
• Participants with a positive hepatitis B core antibody but with negative hepatitis B DNA may be considered for participation, but must agree to receive appropriate hepatitis B antiviral therapy while on rituximab and have hepatitis B DNA monitored with real-time PCR by the treating physician. These patients should be referred to a hepatologist or gastroenterologist for appropriate monitoring and management.
• Hepatitis C: Patients with positive hepatitis C serology unless HCV RNA is confirmed negative by PCR.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• BeOne Medicines: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, B-Cell

Interventions

zanubrutinib; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sameh Gaballa, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Corona

CONTACT

813-745-3465; Richard.Corona@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: April 5, 2024
• Study Start: April 19, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)