Multicentre Phase II Trial of Bendamustine in Combination With Rituximab for Patients With Previously Untreated or Relapsed Chronic Lymphocytic Leukemia. CLL2M Protocol of the German CLL-Study Group (GCLLSG)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 195
- 试验地点
- 58
- 主要终点
- Overall response rate
研究概览
简要总结
CLL2M is a phase 2, multicenter, open label study to investigate the possible therapeutic benefits of using bendamustine in combination with rituximab for the treatment of patients with previously untreated or relapsed CLL.
详细描述
Conventional chemotherapy and also high dose chemotherapy with autologous stem cell transplantation are not curative treatment options in B-CLL; nearly all patients will eventually relapse. Also monoclonal antibodies are not curative for B-CLL patients in monotherapy, their impact on survival in combination with conventional chemotherapy is currently validated. In addition, there is no standard combination therapy for patients with relapsed CLL. Therefore there is an urgent medical need to identify new strategies.
The combination of rituximab (monoclonal antibody) and bendamustine (chemotherapy) has shown encouraging activity in patients with relapsed/refractory NHL or mantle cell lymphoma. In vitro studies have been used to investigate the effects of bendamustine and rituximab on programmed cell death (apoptosis) and have shown synergistic effects of both drugs. The mechanisms of action of these two active drugs may provide a treatment with good therapeutic potential in CLL. However, though bendamustine has been used for over 30 years there is still a need to define a standard regimen for the use of bendamustine in combination with monoclonal antibodies (mAb) especially in the treatment of CLL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •18 years of age or older
- •Diagnosis of B-CLL in need of treatment
- •Previously untreated Binet stage C or Binet B with need of treatment according to NCI-criteria
- •Relapsed or refractory disease after at least one but not more than 3 prior regimens. Patients who previously received bendamustine must have had at least a partial response with duration of response of at least six months.
- •World Health Organization performance status of 0-2
- •Life expectancy >12 weeks
- •Anti-cancer therapy, major surgery, or irradiation was completed >3 weeks before registration in this study. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
- •Serum creatinine ≤1.5 the institutional upper limit of normal (ULN) or Creatinine clearance >30 ml/min/1.73 m²
- •Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 the institutional ULN value, unless directly attributable to the patient's tumor.
- •Female patients with childbearing potential must have a negative serum pregnancy test within two weeks of first dose of study drug(s). Male and female patients must agree to use an effective contraceptive method while on study treatment and for a minimum of six months following study therapy.
- •Signed, written informed consent.
排除标准
- •Previously treated with >3 prior regimens for B-CLL.
- •Known central nervous system (CNS) involvement with B-CLL.
- •Patients who have progressed with more aggressive B-cell cancers such as Richter's syndrome.
- •History of anaphylaxis following exposure to monoclonal antibodies.
- •Known to be human immunodeficiency virus (HIV), hepatitis B, or C positive.
- •Active infection or history of severe infection (grade 4) within 3 months prior to study registration.
- •Medical condition requiring prolonged use of oral corticosteroids (> 1 month).
- •Use of investigational agents within 30 days prior to study randomization.
- •Active secondary malignancy.
- •ANC <1.5x109/L or platelet count <75x109/L, unless due to bone marrow involvement of CLL.
- •Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (Class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (chronic obstructive pulmonary disease [COPD] with hypoxemia), or major organ malfunction (liver, kidney) that could interfere with the patient's ability to participate in the study.
- •Pregnant or nursing women.
- •Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
- •Participation in another clinical trial
研究组 & 干预措施
Bendamustine plus Rituximab
干预措施: Bendamustine (Drug)
Bendamustine plus Rituximab
干预措施: Rituximab (Biological)
结局指标
主要结局
Overall response rate
时间窗: 56 days after the last of six cycles
Response will be assessed using clinical examination, hematology, bone marrow examination, plain radiograph of the chest (chest X-ray), ultrasound or CT of the abdomen, and MRD testing (for the molecular response rate only).
次要结局
未报告次要终点