A Multi-Center, Open Label, Single Arm, Multiple Dose Study to Assess the Pharmacokinetics of RO5072759 in Chinese Patients With CD20+ Malignant Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 主要终点
- Area Under the Serum Concentration Time Curve From Zero to Day 7 (AUC0-7) of Obinutuzumab on Day 1, Cycle 1
研究概览
简要总结
This multi-center, open-label, single-arm study will evaluate the pharmacokinetics and safety of obinutuzumab in participants with cluster of differentiation (CD) 20 positive (+) malignant disease. Participants will receive multiple doses of obinutuzumab. The anticipated time on study treatment is 24 weeks.
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
- •Diagnosis of CD20+ B-cell lymphoma or B-CLL
- •Refractory/relapsed CLL, FL, and DLBCL
- •At least 1 measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension) with the exception of CLL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy >6 months
排除标准
- •Prior use of any investigational antibody therapy within 6 months of study start
- •Prior use of any anti-cancer vaccine
- •Prior administration of rituximab within 3 months of study start
- •Prior administration of radioimmunotherapy 3 months prior to study entry
- •Central nervous system lymphoma
- •History of other malignancy
- •Evidence of significant, uncontrolled concomitant disease
- •Abnormal laboratory values
- •Patients with progressive multifocalleukoencephalopathy (PML)
- •Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
研究组 & 干预措施
CLL: 1000 mg Obinutuzumab
Participants with chronic lymphocytic leukemia (CLL) will receive 1000 milligrams (mg) obinutuzumab as an intravenous (IV) infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. The first infusion on Cycle 1 Day 1 will be given over two days: Day 1 and Day 2. Additional doses of obinutuzumab will be administered on Cycle 1 Day 8 and Day 15.
干预措施: Obinutuzumab (Drug)
DLBCL: 1000 mg Obinutuzumab
Participants with diffuse large B-cell lymphoma (DLBCL) will receive 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab will be administered on Cycle 1 Day 8 and Day 15.
干预措施: Obinutuzumab (Drug)
FL: 1000 mg Obinutuzumab
Participants with follicular lymphoma (FL) will receive 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab will be administered on Cycle 1 Day 8 and Day 15.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Area Under the Serum Concentration Time Curve From Zero to Day 7 (AUC0-7) of Obinutuzumab on Day 1, Cycle 1
时间窗: Cycle 1-NHL: within 2 hours (h) pre-dose (Pr-D), end of infusion (EoI), 4, 24, 72 and 120 h post-infusion (Po-I) on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8
DLBCL and FL are sub-types of Non-Hodgkin's Lymphoma (NHL) and time frame for these 2 groups was presented under NHL. For CLL, pharmacokinetic (PK) parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.
Maximum Observed Serum Concentration (Cmax) of Obinutuzumab on Day 1, Cycle 1
时间窗: Cycle 1-NHL: within 2 h Pr-D, EoI, 4, 24, 72 and 120 h Po-I on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8
DLBCL and FL are sub-types of NHL and time frame for these 2 groups was presented under NHL. For CLL, PK parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.
Area Under the Serum Concentration Versus Time Curve From 0 to Day 21 (AUC0-21) of Obinutuzumab at Cycle 8
时间窗: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
Cmax of Obinutuzumab at Cycle 8
时间窗: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
次要结局
- Time to Maximum Observed Serum Concentration (Tmax) of Obinutuzumab at Cycle 8(Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1)
- Volume of Distribution at Steady State (Vss) of Obinutuzumab at Cycle 8(Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1)
- Total Systemic Clearance at Steady State (CLss) of Obinutuzumab at Cycle 8(Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1)
- Minimum Observed Serum Concentration of Obinutuzumab(Within 2 hours Pr-D on Day 1 of Cycles 2-8 and on Days 8,15 of Cycle 1)
- Percentage of Participants With Complete Response (CR), CR Unconfirmed (CRu) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria(1 month after the last dose (received on Day 148) of study drug)
- Percentage of Participants With Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria(1 month after the last dose (received on Day 148) of study drug)
- Apparent Terminal Half-life (t1/2)(Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1, 4-week follow-up (Day 29), 3 and 6 months after Cycle 8 dosing)
- Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria(From screening to up to 1 month after the last dose (received on Day 148) of study drug)
- Percentage of Participants With Best Overall Response (BOR) of CR, CRu at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria(From screening to up to 1 month after the last dose (received on Day 148) of study drug)
- Percentage of Participants With Complete Remission (CRe), CRe With Incomplete BM Recovery (CRi) at End of Treatment (1 Month After Cycle 8) in CLL Participants According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines(2 months after the last dose (received on Day 148) of study drug)
- Percentage of Participants With PR, SD, and PD at End of Treatment (1 Month After Cycle 8) in CLL Participants According to IWCLL 2008 Guidelines(2 months after the last dose (received on Day 148) of study drug)
- Percentage of Participants With BOR of CRe, CRi at Anytime During the Study in CLL Participants According to IWCLL 2008 Guidelines(From screening to up to 2 months after the last dose (received on Day 148) of study drug)
- Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in CLL Participants According to IWCLL 2008 Guidelines(From screening to up to 2 months after the last dose (received on Day 148) of study drug)
- Number of Participants With Positive Human Anti-Human Antibodies (HAHA)(Cycle 1 (Day 1), Cycle 4 (Day 1), 4-week follow-up, 3 and 6 month follow-up)
- Number of Participants With Positive Human Anti-Chimeric Antibodies (HACA)(Cycle 1, Day 1)
- Number of Participants With B-cell Depletion or Recovery(Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year)
- Duration of Depletion of CD19+ B-cell(Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year)
- Time to Recovery of CD19+ B-cell(Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year)