Single-Arm PharmacoKinetic/PharmacoDynamic and Safety Study of Eryaspase (GRASPA®) for Patients With Hypersensitivity to PEG-Asparaginase, Diagnosed With Ph(-) Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 23
- 主要终点
- Pharmacokinetics ASNase Activity >100 U/L at 14 Days
研究概览
简要总结
Pegylated-asparaginase (PEG-ASP) is an important part of the treatment of childhood acute lymphoblastic leukaemia (ALL). Unfortunately 13% of patients develops allergy and further treatment is impossible. Furthermore, 6% of patients have developed antibodies (silent inactivation) and have no effect of the PEG-ASP treatment. Truncated asparaginase therapy is associated with inferior event-free survival outcomes, in particular relapse in central nervous system (CNS).
Eryaspase is a new formulation of asparaginase encapsulated in erythrocytes. The erythrocyte membrane protects asparaginase against fast degradation and elimination processes. The encapsulation eliminates the direct somatic contact, and it is hypothesized that this provides the potential to prolong the activity of the enzyme and reduce toxicities.
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
- 1 Year 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 1-45 years at diagnosis of ALL.
- •First line non-high risk ALL patients enrolled in NOPHO ALL2008 or ALLTogether pilot protocols including PEG-ASNase regimen.
- •Documented hypersensitivity reaction to PEG-ASNase with either:
- •Clinical allergy to PEG-ASNase (mild/severe). Serum ASNase activity below the lower level of quantification.
- •Karnofsky/Lansky score ≥
- •Ability to understand and willingness to sign a written ICF and to comply with the scheduled visits, treatment plans, laboratory tests and other study procedures. For patients under 18 years of age, either both parents or the legally appointed representatives had to provide consent.
排除标准
- •Philadelphia chromosome positive ALL.
- •Participation in another clinical trial interfering with the study therapy with exception of NOPHO ALL-2008 or ALLTogether pilot protocol. Patients can participate in other clinical trials not interfering with the study drug. In case of doubt this is assessed by the PI.
- •Uncontrolled intercurrent illness including, but not limited to, patients receiving combination antiretroviral therapy or patients with severe or systemic infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Other severe acute/chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
- •Pregnant or lactating females (serum human chorionic gonadotropin pregnancy test at screening). Use of a highly effective contraceptive measure in women of child-bearing potential and sexually active girls that are of child-bearing potential is required (contraceptive measures are specified in section 6.0).
- •Inadequate organ functions, which prohibit further asparaginase administration;
- •History of pancreatitis
- •History of serious hemorrhage or serious thrombosis with prior asparaginase therapy
- •Severe hepatic impairment at the time of administration (bilirubin >3 times ULN, transaminases >10 times ULN)
- •Pre-existing known coagulopathy (e.g. haemophilia)
- •History of grade 3 or higher transfusion reactions or any contraindication to receive blood transfusion. Presence of specific anti-erythrocytes antibodies (auto-antibodies or anti-public antibodies) preventing from getting a compatible packed Red Blood Cells for the patient.
- •Patient under concomitant treatment likely to cause hemolysis.
研究组 & 干预措施
GRASPA
GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity.
干预措施: GRASPA (Drug)
结局指标
主要结局
Pharmacokinetics ASNase Activity >100 U/L at 14 Days
时间窗: 14 days after first infusion
The primary endpoint was the percentage of patients with ASNase activity \>100 U/L at 14 days following the first infusion (nadir). ASNase activity \>100 U/L is considered adequate for complete asparagine depletion in the blood.
次要结局
- Pharmacokinetic Parameters(14 days after fourth infusion)
研究者
Birgitte Klug Albertsen
MD PhD
Aarhus University Hospital