A Double-blind, Parallel-group, Phase III Study to Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in Subjects With Previously Untreated (CD)20-Positive LTB Follicular Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 317
- 试验地点
- 8
- 主要终点
- Best Overall Response Rate (BORR) for Low Tumor Burden Follicular Lymphoma
研究概览
简要总结
The primary objective of the current study is to demonstrate the equivalent efficacy of rituximab (DRL_RI) and MabThera® in subjects with Low Tumor Burden Follicular Lymphoma (LTB-FL).
Also evaluated by Pharmacokinetic, safety, and immunogenicity assessment between a proposed biosimilar (DRL_RI) and the RMP, as an component of clinical study program, and collectively providing the evidence of biosimilarity.
The study will compare the safety and efficacy of DRL_RI vs MabThera in patients with Low Tumor Burden Follicular Lymphoma (LTB-FL). The primary objective is to establish comparative efficacy as measured by ORR up to week 28
详细描述
It is planned to randomise approx. 312 subjects at approximately ≥ 130 study sites worldwide. Subjects with LTB-FL will be randomized to receive either DRL_RI or MabThera®. Till date, 68 patients have been randomized for the study.
The study specific objectives are mentioned below:
Primary Objective:
• To demonstrate the equivalent efficacy of DRL_RI (biosimilar rituximab) and MabThera in subjects with CD20-positive, LTB FL, as measured by overall response rate (ORR) up to Week 28 evaluated in accordance with Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas.
Secondary Objectives:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Subject is Male or female subjects aged ≥18 years of age.
- •Subject is histologically confirmed, Grade 1-3a, previous ly untreated, CD20-pos itive.
- •Subject has Ann Arbor Stage II to IV and ECOG status of 0 to
- •Subject has Low tumor burden follicular lymphoma as per Groupe d'Etude des Lymphomes Folliculaires (GELF) Criteria
- •Subject has at least 1 measurable tumor mass in 2 dimensions, and the mass must be:
- •Nodal lesion >15 mm in the longest dimension; or
- •Noda l lesion >10 mm to he longest dimension; dimens ion and >10 mm in the shortest dimension; or
- •Extra-nodal lesion with both long and short dimensions ≥10 mm.
- •Subject has Life expectancy ≥3 months.
- •If female subject, then subject should be non-pregnant, non-lactating.
排除标准
- •Subject with prior use of rituximab or any CD20 monoclonal antibody for any reason.
- •Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of murine or other foreign origin.
- •Any prior therapy for follicular lymphoma (including but not limited to chemotherapy, radiotherapy) or subjects on chronic supra-substitutive doses of systemic gluco-corticosteriods.
- •Subjects who, in the opinion of the Investigator, require additional concomitant treatment for lymphoma.
- •Evidence of histologic transformation to high grade lymphoma or diffuse large B-cell lymphoma.
- •Subjects with known sero-positivity for or history of active viral infection with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) will be excluded. And if positive for hepatitis B core antibody or hepatitis C virus (HCV) antibody can only be enrolled if HBV - DNA level <20 IU/mL (or 112 copies/mL) and HCV - RNA is negative respectively by PCR test..
- •Subjects who have received a live vaccine within last 3 months of the first administration of study drug.
- •Subjects with history or presence of a medical condition or disease that in the Investigator's opinion would place the subject at an unacceptable risk for study participation.
- •Participation in any clinical study or having taken any investigational therapy (within 2-months of the first dose of study drug.
- •Women of childbearing potential who do not consent to use highly effective methods of birth control.
结局指标
主要结局
Best Overall Response Rate (BORR) for Low Tumor Burden Follicular Lymphoma
时间窗: Month 7 (Week 28)
Best Overall Response Rate (BORR) is defined as the proportion of participants in each treatment group that achieved a best overall response of either Complete response (CR), unconfirmed Complete response (CRu) or Partial response (PR), up to Month 7 (Week 28) based on central radiology review in accordance with the Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas. As per Cheson 1999, response criteria for target lesions and assessed by radiology: Complete response (CR): All lesions with a longest diameter should be regressed to normal size (≤ 15 mm) or short axis regressed to ≤ 10 mm with confirmed Bone marrow normalization; unconfirmed Complete response (CRu): All lesions with a longest diameter should be regressed to normal size (≤ 15 mm) or short axis regressed to ≤ 10 mm with non-confirmed Bone marrow normalization; Partial Response (PR): ≥ 50 % decrease of sum of products of diameter(SPD) of all the target lesions; Overall Response (OR)=CR+CRu+PR.
次要结局
- Overall Response Rate (ORR)(Week 12, Week 28)
- Complete Response Rate(Week 28)
- Complete Response Rate as a Best Response(Week 28)
- Duration of Response (DOR)(Week 52)
- Progression-free Survival (PFS)(Week 52)
- Overall Survival (OS)(Week 52)
- Number of Participants With Adverse Events(From Screening (Day -28 to -1) up to 52 weeks)
- Number of Participants With Positive Anti-drug Antibody (ADA)(On Day 1, Week 2, Week 3, Week 4, Week 12 post dose)