An Open-Label, Phase 1b Study of ACP-196 With and Without Dexamethasone in Subjects With Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Safety Profile of Acalabrutinib With and Without Dexamethasone
研究概览
简要总结
To characterize the safety profile of acalabrutinib with and without dexamethasone in subjects with relapsed or refractory Multiple Myeloma (MM)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Men and women ≥ 18 years of age.
- •A confirmed diagnosis of MM, which has relapsed after, or been refractory to ≥ 1 prior therapy for MM, and is progressing at the time of study entry.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.
排除标准
- •A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk
- •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, gastric bypass, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- •Breast feeding or pregnant
研究组 & 干预措施
Cohort 1
Acalabrutinib 100 mg twice daily (bid) continuously
干预措施: acalabrutinib (Drug)
Cohort 2
Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
干预措施: acalabrutinib (Drug)
结局指标
主要结局
Safety Profile of Acalabrutinib With and Without Dexamethasone
时间窗: From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression.
AEs and SAEs were coded by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA) reporting system. All AEs summarized were treatment-emergent. Summaries were also presented by the severity of the AE (per Common Toxicity Criteria for Adverse Events \[CTCAE\]) and by relationship to study drug as assessed by the investigator. Events of clinical interest (ECIs) selected for dedicated analysis were evaluated using Standardized MedDRA Queries, where available, by SOC, or by Sponsor-defined baskets of MedDRA Adverse Event Grouped Terms (AEGTs). The following ECIs were summarized: Cardiac events (including a subset of atrial fibrillation), cytopenias (anemia, leukopenia, neutropenia, and thrombocytopenia), hemorrhage (including a subset of major hemorrhage), hepatic events, hypertension, infection, interstitial lung disease/pneumonitis, second primary malignancies (second primary malignancies excluding skin), tumor lysis syndrome.
次要结局
- Pharmacokinetic (PK) Parameters Calculated for Acalabrutinib: AUC0-4, AUClast, AUCINF, Cmax, Tmax, λz, t1/2, CL/F, and Vz/F. PK Parameters Calculated for Dexamethasone: Tmax, Cmax, AUC0-4 and AUClast.(On Days 1 and 22: pre-dose, and at 0.5, 0.75, 1, 2, 4, and 6 hours after the morning dose. On Days 8, 15, and 28: pre-dose and 1 hour after the morning dose.)
- Bruton Tyrosine Kinase (BTK) Occupancy(On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.)
- Response Assessed According to Guidelines Proposed by the International Myeloma Workshop Consensus Panel and European Group for Blood and Marrow Transplant(From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression)