An Open-Label, Randomized, Phase 2 Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 70
- 主要终点
- Progression-Free Survival (PFS) in Patients With Non-germinal Center B-cell-like (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL)
研究概览
简要总结
This is a randomized, open-label, multi-center, phase 2 study of RCHOP with or without VELCADE in adult patients with previously untreated non-(Germinal B-Cell-like) GCB Diffuse Large B-cell Lymphoma (DLBCL). The study will determine whether the addition of VELCADE to RCHOP improves progression-free survival (PFS) in patients with non-GCB DLBCL.
详细描述
The drug tested in this study is called bortezomib (VELCADE®). VELCADE® was tested in people who have Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma. This study looked at the efficacy of RCHOP [rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone] with or without VELCADE®.
The study enrolled 206 patients. Participants were enrolled in one of the two open label treatment groups:
- RCHOP
- Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone]
Participants received treatment for up to six, 21-day cycles.
This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 48 months. Participants made multiple visits to the clinic, and were followed for progression free survival and overall survival until patient withdrawal, death, or 2 years after the last participant was enrolled.
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
- •Patients with previously untreated DLBCL that has been sub classified as the non-GCB subtype.
- •At least 1 measurable tumor mass.
- •Availability of paraffin block with sufficient tumor tissue.
- •No evidence of central nervous system lymphoma.
- •Eastern Cooperative Oncology Group (ECOG) performance status of < or equal to
- •Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
- •Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
- •Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
排除标准
- •Diagnosed or treated for a malignancy other than DLBCL within 2 years of first dose or evidence of active malignancy other than DLBCL.
- •Peripheral neuropathy of Grade 2 or greater.
- •Known history of human immunodeficiency virus (HIV) infection, unless receiving highly active antiretroviral therapy (HAART).
- •Active infection requiring systemic therapy.
- •Major surgery within 2 weeks before first dose.
- •Patients with a left ventricular ejection fraction (LVEF) or less than 45%.
- •Myocardial infarction with 6 months of enrollment or evidence of current uncontrolled cardiovascular conditions as described in the protocol.
- •History of allergic reaction/ hypersensitivity attributable to boron, mannitol, polysorbate 80 or sodium citrate dehydrate, or anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab.
研究组 & 干预措施
RCHOP
RCHOP [rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Cyclophosphamide (Drug)
RCHOP
RCHOP [rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Rituximab (Drug)
RCHOP
RCHOP [rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Doxorubicin (Drug)
RCHOP
RCHOP [rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Vincristine (Drug)
Vc-RCHOP
Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Vincristine (Drug)
RCHOP
RCHOP [rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Prednisone (Drug)
Vc-RCHOP
Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Bortezomib (Drug)
Vc-RCHOP
Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Rituximab (Drug)
Vc-RCHOP
Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Cyclophosphamide (Drug)
Vc-RCHOP
Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Doxorubicin (Drug)
Vc-RCHOP
Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m^2 IV infusion, doxorubicin 50 mg/m^2 IV injection and vincristine 1.4 mg/m^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
干预措施: Prednisone (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) in Patients With Non-germinal Center B-cell-like (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL)
时间窗: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm
PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir.
Progression-Free Survival Rate
时间窗: 2 Years (Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)
PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir. The progression-free survival rate is defined as the Kaplan-Meier (KM) estimate of progression-free survival at 2 years.
次要结局
- Overall Survival(Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)
- Overall Response Rate (ORR)(End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment])
- Complete Response Rate(End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment])
- Duration of Response(Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)
- Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Negative Rate(End of Cycle 2 and End of Treatment (Cycle 6) [Median of 16 weeks on treatment])
- Time to Progression (TTP)(Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category(First dose of study drug through 30 days after the last dose of study drug (Up to 26 Weeks))
- Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher(Days 1, 4 and 10 of each cycle and end of treatment visit (Median of 16 weeks on treatment))