Safety of a Maintenance Therapy With Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Chemosensitive Relapsed Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Safety of lenalidomide
研究概览
简要总结
Allogeneic stem cell transplantation (Allo-SCT) in multiple myeloma (MM) remains a controversial topic because of a high risk of relapse and a significant transplant-related mortality (TRM). In an effort to reduce the TRM, most allogeneic transplants in MM are now performed after reduced-intensity conditioning regimens. In these conditions, TRM usually range from 10 to 20%. However, reducing the intensity of the conditioning invariably increases the incidence of relapse to 45 to 60%. As a consequence, post-transplant strategies to reduce the incidence of relapse after reduced-intensity Allo-SCT should be considered and evaluated.
详细描述
Lenalidomide has a significant clinical activity in patients with relapsed or refractory MM and in patients relapsing after Allo-SCT. The mechanisms of action involve immunomodulation, anti-angiogenesis activity, direct anti tumor activity and effects on microenvironment. So far, the experience with lenalidomide after Allo-SCT has been limited to patients with progressive disease. In such patients, some responses are observed but most of them are transient with median progression-free survivals of less than one year. Lenalidomide used as maintenance therapy in patients with persistent rather than progressive disease might be a better approach.
Lenalidomide is interesting in the Allo-SCT setting also because some recent studies focusing on its immunological properties have suggested that the molecule could stimulate the graft versus myeloma effect. First, it has been demonstrated in vitro that lenalidomide can inhibit the proliferation and the suppressor function of regulatory T cells. Secondly, a clinical study using lenalidomide as salvage therapy after Allo-SCT demonstrated an increase of activated T cells and NK cells. Finally, a case report described a patient's response to lenalidomide associated with the development of an acute graft versus host disease.
Taken together, these data suggest that patients with MM who have a persistent disease after a reduced-intensity Allo-SCT might benefit from a post-transplant maintenance strategy with lenalidomide by a direct anti-tumor effect and a stimulation of the graft versus myeloma effect. The primary objective of this study is to evaluate the safety of such a strategy.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 to 65 years
- •Multiple Myeloma in 2nd or 3rd complete or partial response*
- •Disease never refractory to lenalidomide
- •Lenalidomide treatment ≤ 9 months
- •HLA related or unrelated donor (matched 10/10 or mismatched 9/10 HLA-C high resolution level or HLA-DQ high or low resolution level)
- •Insured under Social Security
- •Information and consent signed
排除标准
- •Stable or progressive disease
- •Hypersensitivity to lenalidomide or excipients
- •Lenalidomide treatment > 9 months
- •Absence of efficient contraception in women or men
- •Cardiac insufficiency (ejection fraction < 50% by echocardiography)
- •Pulmonary disease characterized by DLCO < 60%
- •Severe renal insufficiency (clearance of creatinin < 30 ml/min)
- •Hepatic disease characterized by ASAT and/or ALAT and/or total bilirubin > 2 times the upper normal value except in case of Gilbert's disease
- •Bacterial, Viral or Fungal uncontrolled infections
- •No contraceptive method for Female subjects of childbearing potential
- •No use of condoms for males subjects
- •Pregnant or breast feeding woman
- •History of previous cancer (other than myeloma) except if the patient is in complete remission for more than 5 years.
研究组 & 干预措施
lenalidomide
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Safety of lenalidomide
时间窗: 1 year
The main judgement criteria will be the occurrence of adverse events (AE) requiring the definitive interruption of lenalidomide : * Grade 3 or 4 adverse event according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 occurring at the lowest dose of lenalidomide or * Steroid-refractory acute (Seattle criteria) or chronic (National Institutes of Health (NIH) criteria) graft versus host disease or * Transplant-related death
次要结局
- One-year Overall Survival(one year)
- Incidences of acute and chronic Graft versus Host Disease(one year)
- Immunophenotypic analysis of blood B, T, NK and dendritic cells(one year)
- One-year incidence of Relapse/Progression(one year)
- One-year Progression-Free Survival(one year)
- One-year Transplant Related Mortality(one year)
- Chimerism analysis(one year)
- safety of lenalidomide(one year)