A Multicenter, Open, Randomized, Controlled Phase IIb Trial Evaluating Efficacy and Tolerability of GRASPA (L-asparaginase Encapsulated in Red Blood Cells, Eryaspase) Plus Low-dose Cytarabine vs Low-dose Cytarabine Alone, in Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Elderly Patients, Unfit for Intensive Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 123
- 试验地点
- 21
- 主要终点
- Overall Survival
研究概览
简要总结
The protocol aims at adding GRASPA (L-asparaginase encapsulated in red blood cells, eryaspase) to standard chemotherapy (low-dose cytarabine) to treat patients older than 65 years diagnosed with AML and unfit for intensive chemotherapy.
详细描述
L-asparaginase (ASNase) holds a key role in chemotherapy for Acute Lymphoblastic Leukemia (ALL) in children and young adults. In elderly patients, its efficacy is counterbalanced by its toxicity, which impairs its use. However, a study conducted with GRASPA (L-asparaginase encapsulated in red blood cells, eryaspase) in elderly ALL (study reference "GRASPALL-GRAAL SA2 2008") showed that efficacy/safety profile was positive, paving the way for introducing ASNase benefit into chemotherapy for elderly patients.
In adults, Capizzi (1988) reported a significant benefit of ASNase associated with high-dose cytarabine treatment (HiDAC) in Acute Myeloid Leukemia (AML). Indeed, there was an overall statistically superior complete remission rate for HiDAC/ASNase (40%) vs HiDAC (24%) and an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks vs 15.9 weeks).
Another study in elderly patients also displayed positive results for ASNase treatment (Petti, 1989), as well as recent single case reports that point out the potential benefit of ASNase in different AML or mixed lineage leukemia (Horikoshi, 2009; Rubnitz, 2009).
Our preclinical results also showed that an AML cell line and blast cells from the bone marrow of AML patients were sensitive to ASNase in vitro.
However, up to now, the toxicity of ASNase for elderly had prevented its use in this population that represents the majority of AML patients.
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
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GRASPA
patients will receive one injection of GRASPA (100 IU/kg) after each course of low-dose cytarabine (see Arm "Control")
干预措施: GRASPA (Drug)
结局指标
主要结局
Overall Survival
时间窗: Each patient will be followed for a duration of 24 months.
OS is defined as the time elapsed between randomization and death from any cause.
次要结局
- Response to Treatment(Each patient will be followed for a duration of 24 months.)
- Asparagine Synthetase (Optional)(Until patient stops treatment (expected average of 8 months))
- Patient Quality of Life(Each patient will be followed for a duration of 24 months.)
- Relapse Free Survival(Each patient will be followed for a duration of 24 months.)
- Percentage of Patients Who Need Transfusions(Until patient stops treatment (expected average of 8 months))
- Safety of GRASPA Adverse Events and Serious Adverse Events(Each patient will be followed for a duration of 24 months.)
- Number of Hospitalizations(Each patient will be followed for a duration of 24 months.)
- Progression Free Survival (PFS)(Each patient will be followed for a duration of 24 months.)
- Pharmacodynamic and Pharmacokinetic Parameters of GRASPA(Until patient stops treatment (expected average of 8 months))
- Immunogenicity(Until patient stops treatment (expected average of 8 months))
- Biomarker Cytogenetic Testing (Optional)(Until patient stops treatment (expected average of 8 months))