Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 151
- 试验地点
- 10
- 主要终点
- Event free survival
研究概览
简要总结
This phase II trial studies how well tretinoin and arsenic trioxide with or without gemtuzumab ozogamicin works in treating patients with previously untreated acute promyelocytic leukemia. Drugs used in chemotherapy, such as tretinoin and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotoxins, such as gemtuzumab ozogamicin, may find certain cancer cells and kill them without harming normal cells. Giving tretinoin and arsenic trioxide together with gemtuzumab ozogamicin may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Assess whether a combination of all-trans retinoic acid (ATRA [tretinoin]), and arsenic trioxide (ATO) can produce long-term event-free survival in patients with low-risk untreated acute promyelocytic leukemia (APL).
II. Assess whether administration of gemtuzumab ozogamicin (GO) at the diagnosis in patients with high-risk APL (white blood cell [WBC] > 10,000) and if the WBC rises to > 10,000 after start of treatment (in patients with low-risk disease) will improve complete response (CR) rate without increasing toxicity in high-risk untreated APL.
OUTLINE:
INDUCTION: Patients receive tretinoin orally (PO) twice daily (BID), arsenic trioxide intravenously (IV) over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4.
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
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of APL based on the presence of the PML-RAR-alpha fusion gene by cytogenetics, polymerase chain reaction (PCR), or POD test
- •Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study
- •Patients in whom therapy for APL was initiated on an emergent basis are eligible (patients may have already started treatment with ATRA, ATO, and/or one dose of idarubicin due to the urgency to start therapy early)
- •Women of child-bearing potential must have a negative serum pregnancy test at screening; in addition to having a negative pregnancy test confirmed at screening, all female participants of childbearing potential must have a negative pregnancy test confirmed within 48 hours prior to dosing with the study drug
- •All sexually active subjects (males and females of child-bearing potential) agree to use 2 effective methods of contraception for the duration of the study
排除标准
- •Fridericia corrected QT (QTcF) interval on the electrocardiogram (EKG) greater than 480 milliseconds
- •Patients with creatinine > 2.5 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease
- •Patients with total bilirubin >= 2.0 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease
- •Patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease
研究组 & 干预措施
Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide IV over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4.
CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Gemtuzumab Ozogamicin (Drug)
Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide IV over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4.
CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide IV over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4.
CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Arsenic Trioxide (Drug)
Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide IV over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4.
CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Tretinoin (Drug)
结局指标
主要结局
Event free survival
时间窗: The time from the start of treatment to first documentation of disease relapse or death, assessed up to 2 years
Monitored using a Bayesian time-to-event model.
次要结局
未报告次要终点