Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 7
- 主要终点
- Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
研究概览
简要总结
The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. Lenalidomide augments NK cytotoxicity by increasing CD56dimCD3 subset, in addition to inducing IL-2 in T cells. These results provide the cellular and molecular basis for the use of lenalidomide as an adjuvant in immunotherapeutic strategies of monoclonal antibodies (mAb)-based therapies. The combination lenalidomide-rituximab was tested in lymphoma cell lines but not specifically on CLL cell lines. However the observed synergism was attributed to NK cells expansion, thus lending support to the notion that this synergism may operate in other B-cell lymphoproliferative malignancies.
The objective was to develop a non-cytotoxic and effective treatment for CLL that would fulfill an unmet medical need, as a significant proportion of CLL patients are elderly and frail. These patients experience an excess in chemotherapy induced toxicity, often preventing the completion of the planned treatment.
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
- •Recurrent and refractory CLL patients that have received at least one previous treatment with purine analogs.
- •Adequate liver function and renal function.
- •ECOG performance status ≤
- •Signed informed consent
- •Male and female patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy.
排除标准
- •Positive serological markers for hepatitis B with the exception of HBsAc in previously vaccinated patients
- •Pregnant patients
- •HIV infection
- •Concurrent chemotherapy or immunotherapy
- •Other malignancy within the last 2 years, except for localized cutaneous carcinoma
- •Neurological impairment precluding understanding of protocol and the entailed visits and procedures.
- •Patients with Renal insufficiency that requires dialysis.
研究组 & 干预措施
Lenalidomida, Rituximab
Phase I: Lenalidomide will be administered from day 1 to 21 of 28 days cycles, escalating doses (from 2,5mg to 25 mg).Rituximab dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles).
干预措施: Lenalidomida and Rituximab (Drug)
结局指标
主要结局
Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
时间窗: 5 months
6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression. Module I: patients on every cohort will have the same dose during treatment, except if they experiment DLT, in which case dose will be decreased (unless they are on the first dose level).
次要结局
- To determine the time to treatment failure.(5 months)
- To determine the toxicity profile of LenRtx.(5 months)
- To determine the clinical response rate (combined morphological and flow cytometry criteria).(5 months)
- To determine the molecular response rate.(5 months)