Phase III,Open-label,Prospective,Two-armed,Multicenter Study Comparing Zevalin Regimen With no Further Treatment in Patients With Diffuse Large B-cell Lymphoma.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 68
- 试验地点
- 4
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study treats patients with diffuse large B-cell lymphoma whose disease is in complete remission due to previous treatment with Cyclophosphamide Doxorubicin hydrochloride Vincristine Prednisolone- Rituximab (CHOP-R). Half of the patients received Zevalin and the other half receive no further anti-cancer treatment. The two patient groups compared to determine if Zevalin given after CHOP-R therapy provides greater benefits than receiving no additional anti-cancer therapy after CHOP-R.
详细描述
The objectives of this study were to evaluate the efficacy and safety of the Zevalin study regimen compared with observation alone in patients with complete remission (CR or CRu) after first-line CHOP-R, the study was to include patients 60-years-of-age or older with histologically confirmed Ann Arbor stage II, III, or IV diffuse large B-cell lymphoma
End Points:
Primary endpoint: Overall survival (OS) Secondary endpoints: Disease-free survival (DFS), health-related quality of life (HRQL) as assessed by the patient using standard questionnaires .
Number of Patients :
A total of 400 patients (200 per arm) were planned to be 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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, Ann Arbor stage II, III, or IV Diffuse large B-cell lymphoma (DLBCL) according to the Revised European American Lymphoma(REAL)/World Health Organization (WHO) classification .
- •Central pathology review confirming the DLBCL diagnosis and Cluster of differentiation 20 (CD20) positivity, and no evidence of DLBCL in bone marrow
- •First-line treatment of DLBCL must have been 6 or 8 cycles of standard CHOP chemotherapy in combination with rituximab .
- •Complete remission(CR) or unconfirmed complete remission(CRu) according to the International Workshop Response Criteria for Non Hodgkins Lymphoma (NHL) described by Cheson et al and modified for this study after first-line treatment with CHOP-R. Computerised Tomography (CT) scans of chest, abdomen, pelvis, and neck (if applicable) must have been performed within 6 weeks after the last dose of the last course of CHOP-R. Applicability of the neck CT means that the patient had involvement of the neck region by palpation / physical examination at first diagnosis (pre-CHOP-R).
- •Central radiographic review of the CT scans from before and after first-line treatment with CHOP-R fulfilling the radiological requirements for CR/CRu
- •Patients 60 years of age or older at time of randomization
- •WHO performance status (PS) of 0 to 2 within 1 week of randomization
- •Absolute neutrophil count greater than or equal to 1.5 x 10^9/L within 1 week of randomization
- •Hemoglobin greater than or equal to 10 g/dL within 1 week of randomization
- •Platelets greater than or equal to 150 x 10^9/L within 1 week of randomization
- •Life expectancy of 3 months or longer
- •Written informed consent obtained according to local guidelines
排除标准
- •Presence of any other malignancy or history of prior malignancy except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
- •Prior radioimmunotherapy, radiation therapy, or any other NHL therapy except first-line CHOP-R
- •Presence of gastric, central nervous system or testicular lymphoma at first diagnosis
- •Histological transformation of low-grade non-Hodgkin's lymphoma (NHL)
- •Known seropositivity for hepatitis C virus or hepatitis B surface antigen
- •Known history of Human Immunodeficiency virus (HIV) infection
- •Abnormal liver function: total bilirubin > 1.5 x upper limit of normal (ULN) or Alanine Aminotransferase > 2.5 x ULN within 1 week of randomization
- •Abnormal renal function: serum creatinine > 2.0 x ULN within 1 week of randomization
- •Nonrecovery from the toxic effects of CHOP-R therapy
- •Known hypersensitivity to murine or chimeric antibodies or proteins
- •Granulocyte Colony Stimulating Factor (G-CSF) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) therapy within two weeks (or four weeks if pegylated) prior to screening laboratory sampling
- •Concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes,congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study
- •Male and female patients of child-bearing potential unwilling to practice effective contraception during the study and unwilling or unable to continue contraception for 12 months after their last dose of study treatment
- •Female patients who are pregnant or are currently breastfeeding
- •Treatment with investigational drugs less than 4 weeks before the planned Day 1 or nonrecovery from the toxic effects of such therapy
- •Surgery less than 4 weeks before the planned Day 1 or nonrecovery from the side effects of such surgery
- •Concurrent systemic corticosteroid use for any reason except as premedication in case of known or suspected allergies to contrast media or as premedication for potential side effects of rituximab treatment
- •Unwillingness or inability to comply with the protocol
研究组 & 干预措施
Zevalin
Patients received Zevalin.
Zevalin Therapeutic Regimen:
Day 1: Initial administration of 250 mg/m^2 rituximab, followed immediately by administration of 185 MBq of [111In]-ibritumomab tiuxetan ,in centers where centers where biodistribution imaging or dosimetry had not been required, the first rituximab infusion was given alone.
- Day 7-9: Rituximab 250 mg/m^2, followed immediately by [90Y]-ibritumomab tiuxetan 14.8 MBq/kg given as a slow intravenous push over 10 minutes.
Two treatment days one week apart were followed by a 12-week safety period.
干预措施: Zevalin (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: 5 years or until patient dies or lost to follow up
The primary analysis was based on the full analysis set (FAS). Actually, the prominent efficacy variable OS was analysed in the FAS (identical to the safety analysis set) and Per Protocol Set using Kaplan Meier estimates by treatment group. "Overall survival" was defined as the median time interval (in months)from randomization to death from any cause.This time-to-event variable was censored at the date of the last known follow-up visit (provided that the patient was still alive at that time).
次要结局
- Proportion of Participants With Disease Free Survival (DFS)(5 years or until patient disease progresses or lost to follow up)
- The Health-related Quality of Life (HRQL)(Up to Month 36)