NCT02343120已完成1 期
A Phase I/II, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to Investigate the Safety and Pharmacokinetics of the BTK Inhibitor BGB-3111 in Subjects With B-Cell Lymphoid Malignancies
BeiGene23 个研究点 分布在 6 个国家目标入组 385 人开始时间: 2014年9月4日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 385
- 试验地点
- 23
- 主要终点
- Part 1 and Part 2: Number of Participants With Adverse Events
研究概览
简要总结
This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of BGB-3111 in participants with B-cell lymphoid malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years, voluntarily consented to the study.
- •WHO classification defined B-lymphoid malignancy, with the exception of Burkitt lymphoma/leukemia, plasma cell myeloma, acute lymphoblastic leukemia, lymphoblastic lymphoma, and plasmablastic lymphoma.
- •Requirement for treatment in the opinion of the investigator.
- •Disease which has relapsed, or is refractory, following at least one line of therapy, with no therapy of higher priority available.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Adequate hematologic function, as defined by neutrophils ≥ 1.0 x 10^9/L and platelets ≥ 50 x 10^9/L; participants with neutrophils < 1.0 x 10^9/L due to marrow infiltration are allowed to receive growth factors to bring pre-treatment neutrophils to ≥ 1.0 x 10^9/L.
- •Adequate renal function, as defined by creatinine clearance of ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24 hour urine collection).
- •Adequate liver function, as defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), and bilirubin ≤ 1.5 x ULN (unless documented Gilbert's syndrome).
- •International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
- •Female participants of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, IUD or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
- •Male participants must not donate sperm from initial study drug administration, until 90 days after drug discontinuation.
排除标准
- •Current central nervous system (CNS) involvement by disease
- •Current histologically transformed disease.
- •Prior Bruton's tyrosine kinase (BTK) inhibitor treatment.
- •Allogeneic stem cell transplantation within 6 months, or has active graft-versus-host disease (GVHD) requiring ongoing immunosuppression.
- •Receipt of the following treatment prior to first dose of zanubrutinib: corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 2 weeks, monoclonal antibody within 4 weeks.
- •Not recovered from toxicity of any prior chemotherapy to grade ≤
- •History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
- •Uncontrolled systemic infection requiring parenteral anti-microbial therapy.
- •Major surgery in the past 4 weeks.
- •Known HIV, or active hepatitis B or hepatitis C infection (detected positive by PCR).
- •Cardiovascular disease resulting in New York Heart Association function status of ≥
- •Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease that in the investigator's opinion would adversely impact on his/her participating in the study.
- •Inability to comply with study procedures.
- •On medications which are cytochrome P450 (CYP) 3A inhibitors.
研究组 & 干预措施
Zanubrutinib
Experimental
Participants were administered up to 320 mg total daily dose of zanubrutinib until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Part 1 and Part 2: Number of Participants With Adverse Events
时间窗: Up to approximately 6 years and 7 months
Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements
Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib
时间窗: Month 9
RP2D for zanubrutinib was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 320 mg QD
次要结局
- Part 1 and Part 2: Area Under the Curve From Time 0 to the Last Sampling Time Point Within the Dose Interval (AUClast) of Zanubrutinib(Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours)
- Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib(Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours)
- Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib(Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours)
- Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib(Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours)
- Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib(Week 2 Day 1 pre-dose and 24 hours)
- Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib(Week 2 Day 1 pre-dose and 24 hours)
- Part 1 and Part 2: Progression-free Survival (PFS)(Up to 6 years and 7 months)
- Part 1 and Part 2: Overall Survival (OS)(Up to 6 years and 7 months)
- Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F)(Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours)
- Part 1 and Part 2: Overall Response Rate (ORR)(Up to 6 years and 7 months)
- Part 1 and Part 2: Duration of Response (DOR)(Up to 6 years and 7 months)
- Part 1 and Part 2: Complete Response Rate (CRR)(Up to 6 years and 7 months)
- Part 1 and Part 2: Partial Response (PR) or Better(Up to 6 years and 7 months)
- Number of Participants With Greater Than 75% Bruton's Tyrosine Kinase (BTK) Occupancy(Week 1 Day 1 (W1D1) predose, W1D1 4 hours, W1D2 24 hours, W1D3 predose, and W2D1 predose)
研究者
研究点 (23)
Loading locations...
相似试验
已完成
1 期
Zanubrutinib (BGB-3111) in Combination With Tislelizumab (BGB-A317) in Participants With B-cell MalignanciesLeukemiaLymphomaNCT02795182BeiGene75
已完成
1 期
BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid MalignanciesB-cell Lymphoid MalignanciesNCT02569476BeiGene119
终止
1 期
Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory TumorsSolid TumorB-Raf Mutation-Related TumorsNCT04249843MapKure, LLC109
已完成
2 期
Study of Tislelizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder CancerLocally Advanced or Metastatic Urothelial Bladder CancerNCT04004221BeiGene113
已完成
1 期
A Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Participants With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell LymphomaDiffuse Large B-Cell Lymphoma (DLBCL)NCT05364424Hoffmann-La Roche43