An Escalating Dose Phase IIa Study of L-Asparaginase Encapsulated in Erythrocytes (GRASPA®) in Association With Polychemotherapy During Induction Phase for Treatment of Elderly Patients With Acute Lymphoblastic Leukaemia (ALL), Aged 55 Years and Over, With Philadelphia Chromosome-negative (ALL Ph-)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 主要终点
- Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
研究概览
简要总结
The main purpose of this study is to determine the maximum tolerated and efficient dose of GRASPA® in combination with polychemotherapy treatment of elderly patients with ALL, 55 years and over, Philadelphia chromosome-negative (ALL Ph-).
详细描述
This open label, non randomised, multicentric and national phase IIa study was designed to evaluate the safety and efficacy of GRASPA®, a suspension of red blood cells encapsulating E. Coli L-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the European Working Group on Adult ALL (EWALL) for frontline therapy of patients with ALL Ph-, aged 55 years old and over. Patients with a good performance status (WHO score ≤2) and a newly diagnosed ALL Ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with Granulocyte colony stimulating factor (G-CSF) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses. GRASPA® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open label
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged ≥55 years old
- •With newly diagnosed ALL without prior treatment
- •Capable to receive polychemotherapy (World Health Organization (WHO) performance status ≤2)
- •With or without meningeal disease
- •Having signed an Informed Consent Form
- •Subscribed to social security insurance
排除标准
- •ALL translocation(9;22) and/or BCR-ABL (Breakpoint Cluster Region-Abelson) positive
- •Performance status incompatible with chemotherapy treatment (WHO score >2)
- •Patient presenting with a general or visceral contraindication to intensive treatment including :
- •Cardiac insufficiency defined as Left Ventricular Ejection Fraction <50% of the theoretical value
- •Plasma creatinine concentration 2 times greater than the upper limit of laboratory ranges, except if related to ALL
- •Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) levels 5 times greater than the upper limit of laboratory ranges, except if related to ALL
- •Patient with another evolutive cancer other than ALL
- •Severe evolutive infection, or Human Immunodeficiency Virus (HIV) seropositive or, active hepatitis related to B or C viral infection
- •Prior treatment with L-asparaginase (irrespective of the form)
- •History of grade 3 transfusional incident (life threatening)
- •Patient presenting rare and/or dangerous anti-erythrocyte antibodies thus leading to the unavailability of phenotype compatible Red Blood Cells Concentrate
- •Patient included in another clinical trial during the last 4 weeks
研究组 & 干预措施
GRASPA 50 IU/kg
Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase.
干预措施: GRASPA (Drug)
GRASPA 100 IU/kg
Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
干预措施: GRASPA (Drug)
GRASPA 150 IU/kg
Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
干预措施: GRASPA (Drug)
结局指标
主要结局
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
时间窗: 7 days after the first administration of GRASPA® during Induction 1
The main evaluation criterion is a composite efficacy/toxicity criterion. Efficacy, assessed during induction 1: percentage of patients responding to treatment, i.e. with plasma Asn concentration ≤2µM (depleted), for a duration of at least 7 days after the administration of GRASPA®
Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2
时间窗: Induction 1 and Induction 2
Safety: Toxicity, assessed during Induction 1 and Induction 2: according to NCI-CTCAE v3.0 August 2006, with Dose Limiting Toxicities (DLT) defined as: Grade 2 to 4 pancreatic toxicity, Grade 3 or 4 hepatic toxicity, allergic toxicity or deep cerebral thrombosis, known as potentially related to L-asparaginase; hematological toxicity defined as bone marrow blast free aplasia, 30 days following the last injection of chemotherapy, all other Grade 4 toxicities.
次要结局
- Cerebral Spinal Fluid Concentrations of Glutamic Acid(Induction 1 and Induction 2)
- Number of Patients Positive for Anti-L-asparaginase Antibodies(Induction 1 and Induction 2)
- Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2(1 and 2 months)
- Cerebral Spinal Fluid Concentrations of Glutamine(Induction 1 and Induction 2)
- Summary of Free Asparaginase Over Time(Induction 1 and Induction 2)
- Summary of Encapsulated Asparaginase (U/L) Over Time(Induction 1 and Induction 2)
- Cerebral Spinal Fluid Concentrations of Aspartic Acid(Induction 1 and Induction 2)
- Plasma Concentrations of Asparagine(Induction 1 & Induction 2)
- Plasma Concentrations of Glutamine(Induction 1 and Induction 2)
- Plasma Concentrations of Glutamic Acid.(Induction 1 and Induction 2)
- Cerebral Spinal Fluid Concentrations of Asparagine(Induction 1 and Induction 2)
- Plasma Concentrations of Aspartic Acid(Induction 1 and Induction 2)