Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Occurrence of a Dose-Limiting Toxicity
研究概览
简要总结
This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.
详细描述
Significance
- Substitution of Erwinase after E.coli asparaginase allergy has been standard practice despite the paucity of evidence regarding its efficacy and uncertainty about dose. Definition of an appropriate dose and schedule of Erwinase that provides reliable asparagine depletion may be useful for patients with clinical allergy to E. coli asparaginase, both in first remission or after relapse.
- Patients in relapse may have a different level of asparagine synthesis than patients maintaining remission and require different asparaginase dosing.5
- Intravenous administration provides more rapid and predictable asparagine depletion with less discomfort and danger of bleeding for often thrombocytopenic patients than intramuscular administration.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with first marrow relapse.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with second marrow relapse, if the duration of CR2 > 18 months year.
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 21 Years（Child, 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
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Erwinase (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Vincristine (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Dexamethasone (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Doxorubicin (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Cytarabine (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Methotrexate (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Triple Intrathecal Therapy (Drug)
Single Arm
All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
干预措施: Dexrazoxane (Drug)
结局指标
主要结局
Occurrence of a Dose-Limiting Toxicity
时间窗: Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase
The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy.
次要结局
- Response Rate and Minimum Residual Disease(After completion of treatment course)
- Asparaginase Activity(PK samples to be collected Pre-Tx, and and Erwinase Doses 3, 6 and 9 and Day 29)