An Open-Label, Randomized, Parallel-Group Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 447
- 试验地点
- 128
- 主要终点
- Percentage of Participants With Complete Response (CR) at End of Treatment Period
研究概览
简要总结
The primary objective of the study is to compare the complete response (CR) rate of bendamustine and rituximab (BR) with that of standard treatment regimens of either rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with advanced, indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL).
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
- •Histopathologic confirmation of one of the following cluster of differentiation antigen 20 positive (CD20+) B-cell non-Hodgkin's lymphomas (tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review):
- •follicular lymphoma (NCI CTCAE grade 1 or 2)
- •immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
- •splenic marginal zone B-cell lymphoma
- •extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tumor (MALT) type
- •nodal marginal zone B-cell lymphoma
- •mantle cell lymphoma
- •Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):
- •presence of at least one of the following B-symptoms:
- •fever (>38ºC) of unclear etiology
- •night sweats
- •weight loss of greater than 10% within the prior 6 months
- •large tumor mass (bulky disease)
- •presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma-induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
- •hyperviscosity syndrome due to monoclonal gammopathy
- •CD20+ B cells in lymph node biopsy or other lymphoma pathology specimen.
- •No prior treatment (patients on "watch and wait" may enter the study if a recent biopsy [obtained within the last 6 months] is available)
- •Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:
- •hemoglobin of >= 10.0 g/dL
- •absolute neutrophil count (ANC) >=1.5*10^9/L
- •platelet count >=100*10^9/L
- •Bidimensionally measurable disease (field not previously radiated)
- •Able to provide written informed consent
- •Eastern Cooperative Oncology Group (ECOG) Performance Status <=2
- •Estimated life expectancy >=6 months
- •Serum creatinine of <=2.0 mg/dL or creatinine clearance >=50 mL/min
- •Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤2.5*upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
- •Left ventricular ejection fraction (LVEF) >= 50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with R-CHOP
- •A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
- •Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control.
排除标准
- •Chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), or grade 3 follicular lymphoma
- •Transformed disease (bone marrow blasts are permitted; however, transformed disease indicating leukemic involvement is not permitted)
- •Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma
- •Prior radiation for NHL, except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
- •Active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment
- •New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiograph (ECG) evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months (prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
- •Known human immunodeficiency virus (HIV) positivity
- •Active hepatitis B or hepatitis C infection (hepatitis B surface antigen testing required)
- •Women who are pregnant or lactating
- •Corticosteroids for treatment of lymphoma within 28 days of study entry Chronically administered low-dose corticosteroids (e.g., prednisone ≤20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted
- •Any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to receive therapy
- •Any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data
- •Any other investigational agent within 28 days of study entry
- •Known hypersensitivity to bendamustine, mannitol, or other study-related drugs
- •Ann Arbor stage I disease.
研究组 & 干预措施
Bendamustine and Rituximab (BR)
Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1
干预措施: bendamustine (Drug)
Bendamustine and Rituximab (BR)
Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1
干预措施: rituximab (Drug)
R-CHOP/R-CVP
Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles.
R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5
R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
干预措施: rituximab (Drug)
R-CHOP/R-CVP
Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles.
R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5
R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
干预措施: vincristine (Drug)
R-CHOP/R-CVP
Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles.
R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5
R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
干预措施: prednisone (Drug)
R-CHOP/R-CVP
Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles.
R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5
R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
干预措施: cyclophosphamide (Drug)
R-CHOP/R-CVP
Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles.
R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5
R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
干预措施: doxorubicin (Drug)
结局指标
主要结局
Percentage of Participants With Complete Response (CR) at End of Treatment Period
时间窗: 6 to 8 21 or 28-day cycles (18-32 weeks)
CR=complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present pretherapy; protocol-specified positron emission tomography (PET) scan assessment criteria; (if the spleen and/or liver were enlarged on the basis of physical examination and/or anatomic imaging before treatment) the liver and/or spleen were considered normal size on physical examination and by anatomic imaging after therapy, with disappearance of all nodules related to lymphoma; (if the bone marrow was involved by lymphoma before treatment) the infiltrate must have cleared on subsequent bone marrow biopsies.
次要结局
- Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results(32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit))
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period(32 weeks)
- Worst Overall CTCAE Grade for Hematology Laboratory Test Results(32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit))
- Percentage of Participants With Overall Response at End of Treatment Period(6 to 8 21 or 28-day cycles (18-32 weeks))
- Clinically Significant Abnormal Vital Signs(32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit))
- Potentially Clinically Significant Abnormal Weight(Baseline, Week 32)
- Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period(Week 32)
- Therapeutic Classification of Concomitant Medications(32 weeks)
- Kaplan-Meier Estimate for Progression-free Survival (PFS)(Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period))
- Therapeutic Classification of Prior Medications(prior to start of treatment)
- Change From Baseline to End of Treatment in the Global Health Status Score of the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30)(Day 1 (prior to treatment), 32 weeks)
- Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period(Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period)
- Kaplan-Meier Estimate for Event-free Survival (EFS)(Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period))
- Kaplan-Meier Estimate for Duration of Response (DOR)(Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period))
- Overall Survival (OS)(Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period))
- Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period(Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period)