An Open-label, Multicentre, Nonrandomized, Dose-escalating Phase I/II Study, With a Randomized Phase II Part, to Investigate the Safety and Tolerability of RO5072759 Given as Monotherapy in Patients With CD20+ Malignant Disease.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 134
- 主要终点
- Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study
研究概览
简要总结
The primary objective for the phase I part of the study is to investigate the safety and tolerability of escalating intravenous (IV) doses of obinutuzumab given as monotherapy in participants with CD20+ (tumor-infiltrating lymphocytic) Malignant Disease, including B-cell chronic lymphocytic leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL). The primary objective for the phase II part of the study is to investigate the efficacy and safety of one dose of obinutuzumab in participants with relapsed/refractory CLL and NHL that is, in turn, either indolent (iNHL) or aggressive (aNHL).
It is an open label dose escalating study in phase I and open label in phase II, but the two doses in iNHL & aNHL are randomized (to high or low dose of the same open label treatment). CLL was not randomized as only one dose level was used.
Participants with a response who might gain additional benefit from being treated again in the opinion of the investigator may be enrolled in a Retreatment Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Adult patients, >=18 years of age;
- •Phase 1 only: CD20+ malignant disease (B-cell lymphoma or B-CLL);
- •Phase 2 only: relapsed or refractory indolent NHL, relapsed or refractory aggressive NHL or relapsed or refractory B-CLL
- •Have a clinical indication for treatment as determined by the investigator
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Life expectancy >12 weeks
排除标准
- •Prior use of any investigational antibody therapy or other agent within 6 months of study start;
- •Prior use of any anti-cancer vaccine;
- •Prior use of standard anti-lymphoma/leukemia therapy or radiation therapy within 4 weeks of enrollment;
- •Prior use of MabThera (rituximab) within 8 weeks of study entry;
- •Prior administration of radioimmunotherapy 3 months prior to study entry;
- •Central nervous system (CNS) lymphoma.
研究组 & 干预措施
Phase I, NHL
Participants in this NHL arm received multiple ascending doses between 50 and 2000 mg via intravenous infusion of obinutuzumab.
干预措施: Obinutuzumab (Drug)
Phase I, CLL
Participants in this CLL arm received multiple ascending doses between 400 and 2000 mg via intravenous infusion of obinutuzumab.
干预措施: Obinutuzumab (Drug)
400/400 mg - Phase II, iNHL
Participants in this iNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
干预措施: Obinutuzumab (Drug)
1600/800 mg - Phase II, iNHL
Participants in this iNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
干预措施: Obinutuzumab (Drug)
400/400 mg - Phase II, aNHL
Participants in this aNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
干预措施: Obinutuzumab (Drug)
1600/800 mg - Phase II, aNHL
Participants in this aNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
干预措施: Obinutuzumab (Drug)
1000/1000 mg - Phase II, CLL
Participants in this CLL arm received an intravenous infusion of obinutuzumab 1000 mg on Days 1, 8, and 15 of Cycle 1 and obinutuzumab 1000 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 10 infusions. Each cycle was 21 days.
干预措施: Obinutuzumab (Drug)
Retreated Participants
Participants who might benefit from retreatment who were allowed to be treated again via intravenous infusion of obinutuzumab at the request of the investigator.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study
时间窗: Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)
Dose-limiting toxicities were defined as obinutuzumab-related adverse events occurring within the first 28 days of each administration of obinutuzumab, with the exception of B-cell depletion and lymphopenia which are expected outcomes of treatment with obinutuzumab.
Percentage of Participants With Best Overall Response in Phase II of the Study
时间窗: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
Best overall response (BOR) was defined as the percentage of participants with a complete response (CR) or partial response (PR)
次要结局
- Participants With Event-Free Survival (EFS) in Phase II of the Study(by the end of the follow-up period in Phase II of the study (within 3 years, 4 months))
- Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study(by Cutoff Date: 31 March 2012 (within 3 years, 4 months))
- Progression-free Survival (PFS) in Phase II of the Study(by the end of the follow-up period in Phase II of the study (within 3 years, 4 months))
- Percentage of Participants With Partial Response (PR) in Phase II of the Study(by Cutoff Date: 31 March 2012 (within 3 years, 4 months))
- Duration of Response by Disease Type in Phase II of the Study(by the end of the follow-up period in Phase II of the study (within 3 years, 4 months))
- Area Under the Concentration-time Curve of Obinutuzumab Administered on Day 1 of Cycle 1 in Phase I of the Study(Day 1 of Cycle 1)
- Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study(by the end of Phase II (within 3 years, 4 months))
- Percentage of Retreated Participants With Response(by Cutoff Date: 25 November 2013 (within 4 years, 2 months))
- Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants(at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days))