A Phase I/II Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100) in Relapsed/Refractory Cancers of Children and Young Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 14
- 主要终点
- Phase II: to determine the activity of single agent BCT-100 against relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma in children and young adults as measured by disease response after 8 weeks.
研究概览
简要总结
PARC is an international phase I/II trial evaluating the safety and activity of pegylated recombinant human arginase (BCT-100) in children and young people with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade gliomas (brain cancers).
Currently the outcomes for these patients are poor and the therapeutic options are limited with a significant toxicity burden. Therefore new treatments which work in different ways to standard chemotherapy are urgently needed. Research has shown that arginine (a nutrient) is important in the survival of cancer cells. BCT-100 is a drug which can deplete arginine levels and starve cancer cells - a completely new approach. BCT-100 has been tested in adults and shown to be active with almost no side-effects. This trial will test whether this dose of BCT-100 is also safe and active in children with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma. The trial will also study how BCT-100 is broken down in the body and look for new biological markers of treatment response. Up to 64 children with relapsed cancers will be recruited over 2 years.
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
入排标准
- 年龄范围
- 1 Year 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 1- <25 years old at the time of study registration
- •Histologically confirmed disease in one of the following four groups:
- •Group 1 - Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML)
- •Group 2 - Neuroblastoma Group 3 - Sarcoma
- •Group 4 - High grade glioma (as defined by 2016 WHO CNS classification)
- •Radiological or laboratory evidence of disease progression (during or after completion of first line treatment) or any subsequent recurrence (biopsy at relapse is not mandated).
- •Measurable bone marrow disease (group 1) or at least one evaluable radiological site of disease (group 2, 3 and 4).
- •Adequate liver function defined as a total bilirubin ≤1.5x the upper limit of normal for age and ALT ≤ 3x the upper limit of normal for age
- •Documented negative pregnancy test for female patients of childbearing potential within 7 days of trial entry
- •Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 12 months following treatment discontinuation
- •Written informed consent given by patient and/or parents/legal representative
排除标准
- •Previous treatment with another therapeutic arginine depleting drug (bacterial or human) or arginase inhibitor
- •Presence of any ≥ CTCAE grade 3 clinically significant treatment-related toxicity from prior therapies
- •Pregnant or lactating female
- •Evidence of uncontrolled infection
研究组 & 干预措施
Group 2 - Neuroblastoma
PEG- BCT-100 in patients with Neuroblastoma Starting dose 1600U/Kg IV infusion weekly
干预措施: PEG- BCT-100 (Drug)
Group 1 - Leukaemia
PEG- BCT-100 in patients with Leukaemia Starting dose 1600U/Kg IV infusion weekly
干预措施: PEG- BCT-100 (Drug)
Group 3 - Sarcomas
PEG- BCT-100 in patients with Sarcomas Starting dose 1600U/Kg IV infusion weekly
干预措施: PEG- BCT-100 (Drug)
Group 4 - High Grade Glioma
PEG- BCT-100 in patients with High Grade Gliomas Starting dose 1600U/Kg IV infusion weekly
干预措施: PEG- BCT-100 (Drug)
结局指标
主要结局
Phase II: to determine the activity of single agent BCT-100 against relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma in children and young adults as measured by disease response after 8 weeks.
时间窗: After 8 weeks
Disease response (Complete Response (CR) or Partial Response (PR)) after 8 weeks of treatment with BCT-100
Phase I: to establish the recommended phase II dose (RP2D) of BCT-100 in children and young adults as assessed by dose limiting toxicity (DLT) and complete arginine depletion
时间窗: 28 days
Safety profile as measured by the occurrence/non-occurrence of DLT within 28 days of treatment with BCT-100. o Optimal dose as measured by the complete depletion of arginine. This is defined as AAD \<8μM arginine in the blood after 3 doses of BCT-100.
次要结局
- The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4(28 days after treatment completion)
- Disease response - Leukaemia(Within 1 year)
- Disease response - Sarcoma(Within 1 year)
- Disease response - High Grade Glioma(Within 1 year)
- Disease response - Neuroblastoma(Within 1 year)
- Progression free survival (PFS)(Up to three years after registration)
- Overall survival (OS).(Up to three years after registration)
- Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.(Up to 24 weeks)
- Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.(Up to 24 weeks)
- Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.(Up to 24 weeks)
- Area Under the Curve [AUC], of BCT-100 in the paediatric population.(Up to 24 weeks)
- Duration of adequate arginine depletion in blood.(Up to 24 weeks)
- Duration of adequate arginine depletion in bone marrow .(Up to 24 weeks)
- Duration of adequate arginine depletion in cerebrospinal fluid.(Up to 24 weeks)