A Phase 1b/2 Open Label Study to Evaluate the Safety and Efficacy of TRU-016 in Combination With Bendamustine vs. Bendamustine Alone in Patients With Relapsed Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
研究概览
简要总结
The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL.
详细描述
This study consisted of two parts. The initial dose escalation stage was a Phase 1b study evaluating the safety and tolerability of two doses of TRU-016 administered in combination with bendamustine to patients with relapsed chronic lymphocytic leukemia (CLL). In the randomized Phase 2 stage of the study, the efficacy and safety of the selected dose of 20 mg/kg TRU-016 combined with bendamustine was compared to bendamustine alone. The pharmacokinetics and pharmacodynamics of TRU-016 and the development of antibodies to TRU-016 were evaluated in both phases of the study.
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
- •Diagnosis of relapsed CLL with 1 to 3 prior treatments
- •Demonstrated active disease requiring treatment
- •No prior bendamustine treatment
- •Not refractory to fludarabine or other purines, either as a single agent or in combination
- •Age >/=18 years; male or female
- •Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
- •Creatinine clearance > 40 mL/min
- •Absolute neutrophil count (ANC) >/= 1,200/mm3
- •Platelets >/= 75,000/mm3
- •Lymphocytes >/= 5,000/mm3 in Phase 1b
排除标准
- •Treatment with rituximab or other B-cell depleting agent within 30 days or alemtuzumab within 12 weeks
- •Previous anticancer therapy within 30 days
- •Refractory to prior fludarabine or other purine analog therapy either as a single agent or in combination
- •Receipt of prior bendamustine or TRU-016
- •Receipt of an investigational therapy or major surgery within 30 days
- •Previous or concurrent additional malignancy (some exceptions apply)
- •Any significant concurrent medical diseases or conditions
- •Positive serology for HIV or hepatitis C, hepatitis B surface antigen positive or hepatitis B core antibody positive.
- •Pregnant or breast feeding
- •Drug or alcohol abuse
- •Allergic to mannitol
研究组 & 干预措施
Phase 1: 15 mg/kg TRU-016 + Bendamustine
TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
干预措施: 15 mg/kg TRU-016 and bendamustine (Drug)
Phase 1: 20 mg/kg TRU-016 + Bendamustine
TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
干预措施: 20 mg/kg TRU-016 and bendamustine (Drug)
Phase 2: TRU-016 and bendamustine
TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients
干预措施: TRU-016 and bendamustine (Drug)
Phase 2: Bendamustine
Bendamustine (70 mg/m2), n = 33 patients
干预措施: Bendamustine (Drug)
结局指标
主要结局
Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
时间窗: 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years
Patients had full clinical response assessment monthly during treatment, at the end of treatment (EOT) visit, 30 and 60 days after the EOT visit, and subsequently every 3 months until the earliest of progression of CLL, death, initiation of new therapy, withdrawal from the study, or completion of 18 months of follow-up evaluations. Clinical response assessment included physical examination with measurement of spleen, liver, and lymph nodes, disease-related symptoms, and laboratory measurements, specifically complete blood count (CBC) with differential.
次要结局
- Response Per NCI Criteria(1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years)