A Phase I/II Trial of ABT-751 Combined With Dexamethasone, PEG-asparaginase, and Doxorubicin in Relapsed Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 5
- 主要终点
- Number of Patients That Achieved Complete Response to ABT-751
研究概览
简要总结
This is a phase I/II study of an investigational drug called ABT-751, produced by Abbott Laboratories, given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). The phase I portion of this study is being done to find the highest dose of ABT-751 that can be given safely in combination with other chemotherapy drugs. A safe dose is one that does not result in unacceptable side effects. After a safe dose for ABT-751 given with chemotherapy has been found, the study will add additional patients to find out if ABT-751 (given at the maximal safe dose) when given with additional chemotherapy is an effective therapy for the treatment of children with relapsed ALL. It is expected that approximately 15-35 children and young adults will take part in this study.
详细描述
All patients will receive the 2 courses of chemotherapy unless medical complications prevent the administration of some of the drugs. Treatment for the first 2 courses of therapy will last about 2 months.
Treatment on this study will consist of a combination of 8 anti-cancer medications. The 8 anticancer medicines are ABT-751, dexamethasone, PEG-asparaginase, doxorubicin, cytarabine (Ara-C), methotrexate (MTX), cyclophosphamide, and 6-thioguanine. All the drugs except ABT-751 are well known anti-cancer drugs and have been used extensively in the treatment of cancer.
During the Phase I portion of this study, when you enroll, you will be given an assigned dose of ABT-751. The dose of ABT-751 will be based on doses given in previous studies done with adults and children. At each dose level of ABT-751, between 3 and 6 children will receive ABT-751 in combination with chemotherapy. If the side effects are not too severe, the next group of children will receive a higher dose. The dose will continue to be increased until we find the dose that causes serious side effects. Your dose of ABT-751 will not be increased. If you have bad side effects, your dose may be decreased.
The dose used during the Phase 2 part of this study will be determined by the outcome of the Phase I study. The highest dose used in Phase I that was tolerated without serious side effects will be the one used in Phase 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 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
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level 1
Treatment Dose of ABT-751 is 80 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level 2
Treatment Dose of ABT-751 is 100 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level 3
Treatment Dose of ABT-751 is 125 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level 4
Treatment Dose of ABT-751 is 150 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level 5
Treatment Dose of ABT-751 is 175 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level 0
Treatment Dose of ABT-751 is 65 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: ABT-751 (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Dexamethasone (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: PEG-asparaginase (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Doxorubicin (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cytarabine (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Methotrexate (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: Cyclophosphamide (Drug)
Dose Level -1
Treatment Dose of ABT-751 is 50 mg/m2/day
Tx Course 1:
• ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate
Tx Course 2:
• Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751
Tx Courses 3-12 (maintenance courses):
• ABT-751, IT Methotrexate
干预措施: 6-thioguanine (Drug)
结局指标
主要结局
Number of Patients That Achieved Complete Response to ABT-751
时间窗: Day 29 of Course 1
Complete response (CR) is the occurrence of all of the following on approximately Day 29: less than 5% leukemic blasts in the bone marrow aspirate with no evidence of leukemic blasts in the CSF or peripheral blood and recovery of peripheral blood counts of an Absolute neutrophil count (ANC) \> 750/μL and Platelet count \> 75,000 μL.
Number of Patients That Experienced Dose Limiting Toxicity From ABT-751
时间窗: Each dose level is evaluated
ABT-751 was given daily for 21 days for a period of 28 day course in combination with dexamethasone, PEG-asparaginase, and doxorubicin. The occurrence of a dose limiting toxicity (DLT) was evaluated at the end of the 28 day course. DLT will be defined as any of the following events that are deemed by the investigator as probably or definitely attributable to ABT-751. Toxicity grade follows the CTCAE criteria, version 3.0. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov). * Grade 3 or 4 Ileus * Grade 3 or 4 Constipation * Grade 3 or 4 Gastrointestinal obstruction, any location * Grade 3 or 4 Sensory Neuropathy * Grade 3 or 4 Motor Neuropathy * Grade 3 or 4 Neuropathic pain lasting longer than 24 hours despite medical intervention * Grade 3 or 4 Hypoxia in the absence of anemia or infection * Grade 4 Alanine aminotransferase (ALT) which does not return to
次要结局
- Number of Patients With Occurrence of Toxic Death(From the first dose of study therapy until 30 days after last therapy dose. Last dose protocol therapy is on day 21.)