Rituximab and Zanubrutinib in Patients With Indolent B-cell Lymphomas

Exclusion Criteria

• •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.
• •Documentation of CD20+ status.
• •All participants must have an indication for therapy such as: symptoms attributable to lymphoma, threatened end-organ function, or cytopenia secondary to lymphoma.
• •All participants must be 18 years of age or older.
• •All participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• •All participants must be able to swallow whole pills.
• •All participants must have the ability and willingness to comply with the requirements of the study protocol.
• •All female participants who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy).
• •All female participants of childbearing potential must have a negative serum pregnancy test upon study entry.
• •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.
• •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:
• •2. 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.
• •3. Hepatitis C: Patients with positive hepatitis C serology unless HCV RNA is confirmed negative by PCR.
• •Vaccination with a live vaccine ≤ 28 days prior to the start of treatment.
• •Participants should not have a history of uncontrolled seizures.
• •Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment on the study.
• •Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg at screening.
• •Participants should not have a stroke or intracranial hemorrhage within last 6 months.
• •Participants may not have had major surgery within 28 days of enrollment, or minor surgery within 7 days of enrollment. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician.
• •Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.