A Phase II, Open-Label, Multicenter Study of Efficacy, Safety, and Biomarkers in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma Treated With GA101 (RO5072759) in Combination With CHOP Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 76
- 主要终点
- Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment
研究概览
简要总结
This open-label, multicenter study will evaluate the efficacy and safety of obinutuzumab [RO5072759 (GA101)] in combination with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) chemotherapy in patients with advanced diffuse large B-cell lymphoma. Patients will receive 8 cycles of obinutuzumab (1000 mg intravenously on Day 1 of each 21-day cycle, during Cycle 1 obinutuzumab will also be infused on Days 8 and 15) in combination with CHOP chemotherapy on Day 1 of cycles 1 to 6. A substudy will investigate the drug-drug interaction of obinutuzumab with CHOP chemotherapy agents. For the substudy, an additional cohort of approximately 15 patients are planned to be enrolled at a subset of investigational sites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Previously untreated cluster of differentiation antigen 20 (CD20)-positive diffuse large B-cell lymphoma
- •Ann Arbour Stage III/IV and bulky II (mass >10 cm)
- •At least one bi-dimensionally measurable lesion defined as >1.5 cm in its largest dimension by CT scan
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- •Left ventricular ejection fraction ≥50%
- •Adequate hematologic function
排除标准
- •Transformed lymphoma (follicular IIIB) if previously treated with chemotherapy or immunotherapy
- •Prior therapy for diffuse large B-cell lymphoma except for nodal biopsy or local irradiation
- •Central nervous system (CNS) lymphoma, primary mediastinal large cell lymphoma, primary cutaneous lymphoma, primary effusion lymphoma
- •Patients who received cytotoxic drugs or rituximab as part of their treatment for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody
- •Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
- •Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- •History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix, or malignancy treated with or without curative intent and in remission without treatment for ≥2 years prior to enrolment
- •Positive for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV-1) infection
- •Pregnant or lactating women
研究组 & 干预措施
obinutuzumab + CHOP
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.
干预措施: obinutuzumab (Drug)
obinutuzumab + CHOP
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.
干预措施: cyclophosphamide (Drug)
obinutuzumab + CHOP
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.
干预措施: doxorubicin (Drug)
obinutuzumab + CHOP
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.
干预措施: prednisone (Drug)
obinutuzumab + CHOP
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.
干预措施: vincristine (Drug)
结局指标
主要结局
Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment
时间窗: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Complete response rate is defined as the percentage of participants with Complete Response (CR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the investigator using regular clinical and laboratory examinations, fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT). CR is the disappearance of all evidence of disease.
Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment
时间窗: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Overall response rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the investigator using regular clinical and laboratory examinations, FDG-PET and computed tomography (CT). CR is the disappearance of all evidence of disease. PR is at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites.
次要结局
- Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion(From end of study treatment up to approximately 30 months)
- Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery(Up to approximately 30 months)
- Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment(From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days))
- Progression-Free Survival (PFS) as Assessed by the Investigator(From the first dose of study treatment to PFS assessment (up to 64 months))
- Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab(Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12)
- Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab(Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12)
- Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment(From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days))
- Duration of Response (DOR)(From the response assessment to relapse, progression, or death (up to 64 months))
- Percentage of Participants With Adverse Events as a Measure of Safety(From the first dose of study treatment to end of study (up to 5 years 4 months))
- Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI)(From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days))
- Pharmacokinetics: Clearance (Cl) for Obinutuzumab(Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12)
- Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab(Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12)
- Pharmacokinetics: Area Under the Concentration-Time Curve 7 Day (AUC7day)(Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12)
- Pharmacodynamics: Peripheral Blood CD19-positive B-cell Count(Up to approximately 24 months)