An Open-label, Multicenter, Randomized Phase II Trial Comparing the Efficacy, Safety, and Pharmacokinetics of GA101 1000 mg Versus 2000 mg in Patients With Previously Untreated Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 31
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This open-label, multicenter, randomized study compared the efficacy, safety and pharmacokinetics of obinutuzumab (RO5072759; GA101) 1000 mg versus 2000 mg in participants with previously untreated CLL. Participants were randomized to receive a maximum of 8 cycles (28-day cycle) of obinutuzumab (1000 mg intravenous [IV] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of each subsequent cycle up to 8 cycles or maximum of 8 cycles of obinutuzumab (2000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of each subsequent cycle up to 8 cycles.
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
- •Confirmed diagnosis of CD20-positive B-cell CLL (per International Workshop on Chronic Lymphocytic Leukemia [IWCLL] guidelines)
- •Rai Stage III/IV or Binet Stage C disease, or Rai Stage I/II or Binet Stage B disease that requires treatment according to IWCLL guidelines
- •No previous treatment for CLL chemotherapy, radiotherapy or immunotherapy; no previous rituximab treatment for autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP); prior use of steroids for AIHA or ITP is allowed
- •Eastern Cooperative Oncology Group performance status of 0, 1 or 2
排除标准
- •Confirmed diagnosis of Transformation of CLL to aggressive B-cell malignancy
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- •Evidence of severe, uncontrolled concomitant disease
- •Known active infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks before the start of Cycle 1
- •Seropositive for human immunodeficiency virus (HIV)
- •Positive for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology)
- •Positive for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
- •Pregnant or lactating women
- •Concurrent (or within 7 days prior to first dose of study treatment) systemic corticosteroid use, except for low-dose corticosteroid therapy used to treat chronic medical conditions
研究组 & 干预措施
Obinutuzumab 1000 mg
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
干预措施: Obinutuzumab (Drug)
Obinutuzumab 1000 mg
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
干预措施: Corticosteroids (Drug)
Obinutuzumab 2000 mg
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
干预措施: Obinutuzumab (Drug)
Obinutuzumab 2000 mg
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Week 32
ORR was defined as the percentage of participants with complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR) as assessed by the investigator according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines two months after last treatment. CR required: blood lymphocytes \< 4 x 10\^9/Liter (L), absence of lymphadenopathy (≤ 1.5 centimeter (cm) in long axis by Computed Tomography), no hepatomegaly or splenomegaly, absence of disease, Neutrophils \> 1.5 x 10\^9/L, Platelets \> 100 x 10\^9/L, Hemoglobin \>11 g/dL, bone marrow normal and lymphoid nodules absent. CRi was CR with incomplete marrow recovery. PR required: 50% decrease in peripheral blood lymphocyte count, 50% reduction in lymphadenopathy, 50% reduction of liver and/or spleen enlargement if enlarged at baseline, Neutrophils \> 1.5 x 10\^9/L or \> 50% of pretreatment value, Platelets \> 100 x 10\^9/L or 50% of pretreatment value and Hemoglobin \> 11 g/dL or \> 50% of pretreatment value.
次要结局
- Progression-free Survival (PFS)(Up to 4 years, 5 months)
- Number of Participants Surviving at End-of-Study(Up to 4 years, 5 months)
- Percentage of Participants With Adverse Events of Interest(Up to 4 years, 5 months)
- Duration of Response(Up to 4 years, 5 months)
- PK Parameter: Maximum Serum Concentration (Cmax)(Day 148 (at end of infusion))
- PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt )(Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion))
- Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)(Up to 4 years, 5 months)
- Percentage of Participants With Adverse Events Leading to Study Discontinuation(Up to 4 years, 5 months)
- PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits)(Months 3, 6, 9, and 12)
- Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion(Up to 4 years, 5 months)
- PK Parameter: Clearance at Steady State (CLss)(Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion))
- Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery(Up to 4 years, 5 months)
- PK Parameter: Volume of Distribution at Steady State (Vss)(Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion))
- PK Parameter: Terminal Half-Life (t1/2)(Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion))