A Phase 2 Open-Label, Multicenter Study of Rituximab and Zanubrutinib in Patients With Indolent B-cell Lymphomas
概览
- 阶段
- 2 期
- 干预措施
- Zanubrutinib
- 疾病 / 适应症
- Follicular Lymphoma
- 发起方
- H. Lee Moffitt Cancer Center and Research Institute
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Overall Response Rate: Cohort B
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
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).
研究者
入排标准
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Cohort A: Untreated Marginal Zone Lymphoma
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.
干预措施: Zanubrutinib
Cohort A: Untreated Marginal Zone Lymphoma
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.
干预措施: Rituximab
Cohort B: Untreated Follicular Lymphoma
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.
干预措施: Zanubrutinib
Cohort B: Untreated Follicular Lymphoma
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.
干预措施: Rituximab
结局指标
主要结局
Overall Response Rate: Cohort B
时间窗: Up to 6 Months
Overall response rate will be determined using a 5 point scale per the Lugano criteria.
Overall Response Rate: Cohort A
时间窗: Up to 6 Months
Overall response rate will be determined using a 5 point scale per the Lugano criteria.
次要结局
- Efficacy of Zanubrutinib and Rituximab(Up to 24 months)
- Safety and tolerability of combination Zanubrutinib and Rituximab(Up to 24 Months)