S0535, A Phase II Study of ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin in Patients With Previously Untreated High-Risk Acute Promyelocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 192
- 主要终点
- Continuous Complete Remission at 3 Years
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination chemotherapy may be more effective in treating promyelocytic leukemia.
PURPOSE: This phase II trial is studying how well giving gemtuzumab together with combination chemotherapy works in treating patients with previously untreated promyelocytic leukemia.
详细描述
OBJECTIVES:
- To assess the event-free survival and death during the first six weeks in patients with previously untreated, high-risk acute promyelocytic leukemia treated with a combined regimen of tretinoin, arsenic trioxide, and gemtuzumab ozogamicin.
- To estimate the frequency and severity of toxicities of this regimen in this group of patients.
- To investigate the molecular response rate utilizing this regimen in high-risk patients.
OUTLINE:
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Induction chemotherapy: Patients receive oral tretinoin twice daily beginning on day 1 until CR (up to 90 days), gemtuzumab ozogamicin IV over 2 hours on day 1, and arsenic trioxide IV over 2 hours 5 days a week beginning on day 10 until CR (up to 60 days) in the absence of disease progression or unacceptable toxicity. Patients achieving A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy after maintaining B1 peripheral blood status for ≥ 7 days.
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Consolidation therapy: Beginning between 2-8 weeks after documentation of complete response (CR), patients receive consolidation therapy.
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Consolidation courses 1 and 2: Patients receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks. Treatment repeats every 7 weeks for up to 2 courses. Patients remaining in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status continue with consolidation courses 3 and 4.
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Consolidation courses 3 and 4: Within 4 weeks of completing consolidation course 2, patients receive oral tretinoin twice daily on days 1-7 and daunomycin IV bolus or over 1 hour on days 1-3. Within 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 4 as in course 3. Patients who remain in B1 peripheral blood and C1 extramedullary disease status continue on consolidation courses 5 and 6.
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Consolidation courses 5 and 6: Beginning between 2-8 weeks after recovery to B1 peripheral blood status, patients receive gemtuzumab IV over 2 hours on day 1. Between 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 6 as in course 5. Patients who remain in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to maintenance therapy.
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Maintenance therapy: Beginning 2-8 weeks after recovery of blood counts, patients receive oral tretinoin twice daily on days 1-7 every other week for 1 year, oral mercaptopurine once daily for 1 year, and oral methotrexate once weekly for 1 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
- 18 Years 至 120 Years（Adult, Older 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
Treatment
Induction:
ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
Consolidation 1 and 2:
Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest
Consolidation 2 and 3:
ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3
Consolidation 5 and 6:
GO 9mg/m2 IV D1
Maintenance:
ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year
干预措施: mercaptopurine (Drug)
Treatment
Induction:
ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
Consolidation 1 and 2:
Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest
Consolidation 2 and 3:
ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3
Consolidation 5 and 6:
GO 9mg/m2 IV D1
Maintenance:
ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year
干预措施: arsenic trioxide (Drug)
Treatment
Induction:
ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
Consolidation 1 and 2:
Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest
Consolidation 2 and 3:
ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3
Consolidation 5 and 6:
GO 9mg/m2 IV D1
Maintenance:
ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year
干预措施: gemtuzumab ozogamicin (Drug)
Treatment
Induction:
ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
Consolidation 1 and 2:
Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest
Consolidation 2 and 3:
ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3
Consolidation 5 and 6:
GO 9mg/m2 IV D1
Maintenance:
ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year
干预措施: methotrexate (Drug)
Treatment
Induction:
ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
Consolidation 1 and 2:
Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest
Consolidation 2 and 3:
ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3
Consolidation 5 and 6:
GO 9mg/m2 IV D1
Maintenance:
ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year
干预措施: tretinoin (Drug)
结局指标
主要结局
Continuous Complete Remission at 3 Years
时间窗: 3 years
Binary variable: yes if the patient achieves complete remission and remains in continuous complete remission until at least 3 years after entering the study; otherwise no.
Mortality Rate at 6 Weeks
时间窗: 6 weeks
次要结局
- Frequency of Toxicities(Up to 3 years)