An Open-label, Multi-center, Randomized Study to Evaluate the Efficacy on Tumor Response of GA101 (RO5072759) Monotherapy Versus Rituximab Monotherapy in Patients With Relapsed CD20+ Indolent Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 175
- 主要终点
- Percentage of Participants With Overall Response At the End of Induction Period
研究概览
简要总结
This study will investigate the efficacy of weekly intravenous obinutuzumab [GA101 (RO5072759)] monotherapy, in patients with relapsed CD20+ indolent Non-Hodgkin's Lymphoma. Patients will be randomized to receive either GA101 or rituximab, given as four weekly infusions. At the conclusion of the initial trial patients may be eligible to continue therapy up to 24 months. The anticipated time on study treatment is 3- 24 months, and the target sample size is 100-500 individuals.
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
- •adult patients, >=18 years of age
- •relapsed CD20+ indolent B-cell non-Hodgkin's lymphoma
- •documented history of response of >/= 6 months duration from last rituximab-containing regimen
- •clinical indication for treatment as determined by the investigator
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
排除标准
- •prior use of any investigational monoclonal antibody within 6 months of study start
- •prior use of any anti-cancer vaccine
- •prior use of rituximab within 8 weeks of study entry
- •radioimmunotherapy within 3 months prior to study entry
- •Central Nervous System (CNS) lymphoma or evidence of transformation to high-grade or diffuse large B-cell lymphoma
研究组 & 干预措施
Obinutuzumab
Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
干预措施: obinutuzumab (RO5072759) (Drug)
Rituximab
Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
干预措施: rituximab (Drug)
结局指标
主要结局
Percentage of Participants With Overall Response At the End of Induction Period
时间窗: Randomization to clinical cutoff: 01 September 2011 (Up to 70 days)
Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigator at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.
次要结局
- Percentage of Participants With Complete Response at the End of the Induction Period(Randomization to clinical cutoff : 01 September 2011 (Up to 70 days))
- Percentage of Participants With Partial Response (PR) at the End of the Induction Period(Randomization to clinical cutoff : 01 September 2011 (Up to 70 days))
- Progression-Free Survival (PFS)(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Event Free Survival(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Percentage of Participants With Event Free Survival (EFS) Events(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Percentage of Participants With Progression-Free Survival (PFS) Events(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Obinutuzumab Serum PK Parameter: Terminal Half-Life (t1/2)(Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Number of Participants With Improved Overall Response During the Extended Treatment Period(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax)(Day 1 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours post-infusion), Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Number of Participants With Peripheral Blood B-Cell Recovery(End of last dose + 6 Months Follow-Up)
- Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) [Includes all AEs reported 28 days after last dose and all Related SAEs regardless of time of last dose.])
- Number of Participants With Infusion Related Reactions(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Number of Participants With Human Anti-Human Antibodies (HAHA)(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Duration of Response(Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months))
- Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve (AUClast)(Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Obinutuzumab Serum PK Parameter: Clearance at Steady-State (CLss)(Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve Between Dosing Interval (AUCtau)(Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Number of Participants With Peripheral Blood B-Cell Depletion(Day 22)
- Obinutuzumab Serum PK Parameter: Volume of Distribution at Steady-State (Vss)(Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Obinutuzumab Trough Serum Concentration (Ctrough)(Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion))
- Number of Participants With Human Anti-Chimeric Antibodies (HACA)(Day 1)