A Phase III, Multicenter, Open-Label Randomized Trial Comparing the Efficacy of GA101 (RO5072759) in Combination With CHOP (G-CHOP) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients With CD20-Positive Diffuse Large B-Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,418
- 试验地点
- 235
- 主要终点
- Median Time to Progression-Free Survival (PFS), Investigator-Assessed
研究概览
简要总结
This open-label, randomized, parallel group study will evaluate the efficacy and safety of obinutuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone or prednisone (CHOP) chemotherapy versus rituximab (MabThera/Rituxan) with CHOP in previously untreated participants with cluster of differentiation 20 (CD20)-positive diffuse large B-cell lymphoma (DLBCL). Participants will be randomized to receive either obinutuzumab 1000 milligrams (mg) intravenously (IV) every 21 days or rituximab 375 milligrams per square meter (mg/m^2) IV every 21 days for 8 cycles, in addition to 6-8 cycles of CHOP chemotherapy IV every 21 days. Participants randomized to the obinutuzumab arm will receive an additional two doses on Days 8 and 15 of Cycle 1. Anticipated time on study treatment is 24 weeks.
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
- •Previously untreated CD20-positive DLBCL
- •At least 1 bi-dimensionally measurable lesion (greater than [>]1.5 centimeters [cm] in its largest dimension on the computed tomography [CT] scan)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- •Adequate hematological function
- •Low-intermediate, high-intermediate or high-risk International Prognostic Index (IPI) score (low-risk IPI score: IPI 1 irrespective of bulky disease or IPI 0 with bulky disease, defined as one lesion greater than equal to (>/=) 7.5 cm)
- •Left ventricular ejection fraction (LVEF) >/=50 percent (%) on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram
排除标准
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products or to any component of CHOP or obinutuzumab
- •Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
- •Participants with transformed lymphoma and participants with follicular lymphoma IIIB
- •Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
- •Prior treatment with cytotoxic drugs or rituximab for another condition (for example, rheumatoid arthritis) or prior use of an anti-CD20 antibody
- •Prior use of any monoclonal antibody within 3 months of the start of Cycle 1
- •Corticosteroid use of >30 milligrams per day (mg/day) of prednisone or equivalent, for purposes other than lymphoma symptom control
- •Primary central nervous system (CNS) lymphoma and secondary CNS involvement by lymphoma, mantle-cell lymphoma (MCL), or histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, plasmablastic lymphoma, and primary cutaneous DLBCL
研究组 & 干预措施
Rituximab+Chemotherapy
Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Rituximab (Drug)
Rituximab+Chemotherapy
Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Cyclophosphamide (Drug)
Rituximab+Chemotherapy
Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Doxorubicin (Drug)
Rituximab+Chemotherapy
Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Vincristine (Drug)
Rituximab+Chemotherapy
Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Prednisone (Drug)
Obinutuzumab+Chemotherapy
Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Obinutuzumab (Drug)
Obinutuzumab+Chemotherapy
Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Cyclophosphamide (Drug)
Obinutuzumab+Chemotherapy
Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Doxorubicin (Drug)
Obinutuzumab+Chemotherapy
Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Vincristine (Drug)
Obinutuzumab+Chemotherapy
Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
干预措施: Prednisone (Drug)
结局指标
主要结局
Median Time to Progression-Free Survival (PFS), Investigator-Assessed
时间窗: Baseline up to approximately 6.5 years (up to 31 January 2018)
Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease \[PD\]). Progression-free survival was defined as the time from randomization until the first documented day of disease progression or relapse, using a modified version of the Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least 50% increase in nodal lesions or \>/=50% increase in any node \> 1 centimeter (cm) or \>/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion \> 1.5 cm or \>/= 50% increase in any previously involved node with a diameter \</= 1 cm such that it is now \>1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).
次要结局
- Overall Response Rate (ORR), IRC-Assessed(Baseline up to approximately 4 years and 9 months (up to 29 April 2016))
- Median Time to Overall Survival (OS)(Baseline up to approximately 6.5 years (up to 31 January 2018))
- Median Time to Event-Free Survival (EFS), Investigator-Assessed(Baseline up to death or disease progression, or initiation of new anti-lymphoma treatment (NALT), whichever occurred first, approximately 6.5 years (up to 31 January 2018))
- Median Time to Disease-Free Survival (DFS), Investigator-Assessed(Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018))
- Time to Next Anti-Lymphoma Treatment (TTNALT)(Baseline up to start of next anti-lymphoma treatment or death due to any cause, whichever occurred first, approximately 6.5 years (31 January 2018))
- Duration of Response (DOR), Investigator-Assessed(Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018))
- Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab(Pre-dose (Hour 0) on Cycle (C) 4 Day (D) 1, at end of treatment/early termination (up to Month 6), every 6 months thereafter for 30 months (cycle length = 21 days))
- Median Time to Progression-Free Survival (PFS), Independent Review Committee (IRC)-Assessed(Baseline up to approximately 4 years and 9 months (up to 29 April 2016))
- Overall Response Rate (ORR), Investigator-Assessed(Baseline up to approximately 6.5 years (up to 31 January 2018))
- Complete Response (CR) at the End of Treatment, Investigator-Assessed(Baseline up to approximately 6.5 years (up to 31 January 2018))
- Complete Response (CR) at the End of Treatment, IRC-Assessed(Baseline up to approximately 4 years and 9 months (up to 29 April 2016))
- Percentage of Participants With Adverse Events (AEs)(Baseline up to approximately 6.5 years (up to 31 January 2018))
- Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale Score(Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to approximately 6.5 years, (cycle length = 21 days))
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores(Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to data cut-off, up to approximately 6.5 years, (cycle length = 21 days))
- Serum Concentrations of Obinutuzumab in Japanese Participants With Diffuse Large B-Cell Lymphoma (DLBCL)(C1: D1 post-infusion and 20-28 and 66-80 hours after end of infusion, D8 and D15 pre-and post-infusion; C2: D1 pre- and post-infusion; C4: D1 pre- and post-infusion; C6: D1 pre- and post-infusion; C8: D1 pre- and post-infusion (cycle length = 21 days))