A Phase I Study to Determine the Safety and Pharmacokinetics of Intravenous Erwinia Chrysanthemi Asparaginase in Patients With Newly Diagnosed Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Aged 60 Years or Older
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- proportion of patients who have a dose limiting toxicity (DLT)
研究概览
简要总结
The purpose of this study is to test the safety of Erwinia Chrysanthemi asparaginase when used alone and together with chemotherapy and find out what effects, if any, it has on people.
详细描述
The study consists of three treatment phases.
- Steroid prophase (days -3 to -1):
To prevent rapid leukemia progression and reduce tumor load, patients will receive either prednisone 60mg/m2 oral daily or equivalent corticosteroid daily for 3 days. 2. Asparaginase phase (days 1 - 14):
Patients will receive Erwinia asparaginase 25,000 IU/m2 IV three times a week on a Monday, Wednesday, Friday (MWF) schedule for 2 weeks. Patients are permitted to begin Erwinia asparaginase on Monday, Wednesday, or Friday, so that their schedules are defined as MWF, WFM, or FMW. For rapid progression of disease (defined by rising WBC >30K with > 50% peripheral blasts), prednisone 60mg/m2 oral daily or equivalent corticosteroid daily may be added.
Bone marrow aspirate and/or biopsy will be performed on days 13-15 of the asparaginase treatment for early disease response assessment. 3. Chemotherapy phase (days 15 - 42):
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 60 years or older
- •Previously untreated Philadelphia chromosome negative acute lymphoblastic leukemia
- •No prior treatment for ALL, except steroids or hydroxyurea (stopped within 24 hour before start of protocol treatment)
- •Serum creatinine ≤ 2 x upper limit of normal (ULN)
- •Adequate liver function, including total bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) ≤ 5 x ULN. If organ function abnormalities are considered due to leukemic infiltration, total bilirubin must be ≤ 2 x ULN.
- •ECOG performance status ≤3
- •Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for a minimum of 90 days after the last dose of treatment on protocol. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential should meet at least one of the following criteria:
- •Have undergone hysterectomy or bilateral oophorectomy; or
- •Have medically confirmed ovarian failure; or
- •Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause
排除标准
- •Lymphoblastic crisis of CML
- •Mature B cell (Burkitt's) ALL
- •Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion.
- •Pregnant women or women who are breast-feeding
- •Concurrent active malignancy requiring immediate therapy
- •Patients with human immunodeficiency virus (HIV)
研究组 & 干预措施
Erwinia Chrysanthemi asparaginase
This is a phase I trial designed to assess the safety of IV Erwinia Chrysanthemi asparaginase during initial induction in patients aged 60 years or older with newly diagnosed Ph-negative ALL. A total of 12 patients will be accrued to the study.
干预措施: Erwinia Chrysanthemi asparaginase (Drug)
结局指标
主要结局
proportion of patients who have a dose limiting toxicity (DLT)
时间窗: with in 6 weeks of starting the study drug
DLTs are defined as any of the following: grade 4 pancreatitis, grade 4 hemorrhage, grade 4 thromboembolism, grade 4 hyperbilirubinemia and any grade 5 toxicity attributable (definitely, probably or possible) to Erwinia asparaginase.
次要结局
未报告次要终点