Risk Adapted Treatment of Newly Diagnosed Childhood Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide (Trisenox® ) During Consolidation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 106
- 试验地点
- 121
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
This phase III trial is studying combination chemotherapy to see how well it works in treating young patients with newly diagnosed acute promyelocytic leukemia. 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. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To decrease the total anthracycline dose from the best current published results in standard risk childhood acute promyelocytic leukemia (APL) while still maintaining a comparable event-free survival (EFS).
SECONDARY OBJECTIVES:
I. To assign treatment based on risk stratification by white blood cell count (WBC) at diagnosis.
II. To estimate the induction failure rate, toxic death rate, disease-free survival rate and overall survival rate in both standard and high risk APL patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be newly diagnosed with a clinical diagnosis of acute promyelocytic leukemia initially by morphology (bone marrow or peripheral blood); bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted; APL is considered a hematological emergency and treatment should be initiated as quickly as possible without waiting for molecular or cytogenetic/fluorescence in situ hybridization (FISH) confirmation; for patients who are unable to begin receiving ATRA in a timely manner following a presumed diagnosis of APL, consideration should be given to initiating ATRA and proceeding with treatment outside of the AAML0631 protocol; if the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate PML-RARA and/or RARA-PML transcripts by RQ-PCR to be eligible; patients without evidence of APL by bone marrow or peripheral blood morphology but with isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis) are eligible provided that the t(15;17) translocation is documented on either marrow or tumor tissue by cytogenetics, FISH, or PCR prior to study enrollment; in this situation, touch preps from the tumor site can be evaluated by FISH with PML-RARA probes; NOTE: A lumbar puncture is not required to be enrolled on study; if the diagnosis of APL is known or suspected, extreme caution must be exercised in performing a lumbar puncture during active coagulopathy; in addition a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma if central nervous system (CNS) disease is suspected or proven; if CNS disease is documented, patients are still eligible
- •No minimal performance status criteria
- •The patient must not have received systemic definitive treatment for APL or other suspected leukemia, including cytotoxic chemotherapy, retinoids, or arsenic; prior therapy with corticosteroids, hydroxyurea, or leukopheresis will not exclude the patient; if a patient received intrathecal cytarabine prior to the diagnosis of APL being known, the patient will still be eligible as long as they meet all other eligibility requirements
排除标准
- •Pregnant women or nursing mothers are excluded; treatment under this protocol would expose an unborn child to significant risks; patients should not be pregnant or plan to become pregnant while on treatment; women and men of reproductive potential should agree to use an effective means of birth control; there is an extremely high risk of fetal malformation if pregnancy occurs while on ATRA in any amount even for short periods
- •Patients with a pre-existing prolonged QT Syndrome will not be eligible for this protocol due to the use of arsenic trioxide which can prolong the QT interval
研究组 & 干预措施
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Idarubicin (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Arsenic Trioxide (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Cytarabine (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Idarubicin (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Mercaptopurine (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Methotrexate (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm I (standard risk, combination chemotherapy)
See Detailed Description
干预措施: Tretinoin (Drug)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Arsenic Trioxide (Drug)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Cytarabine (Drug)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Mercaptopurine (Drug)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Methotrexate (Drug)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm II (high risk, combination chemotherapy)
See Detailed Description.
干预措施: Tretinoin (Drug)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: At 3 years from study entry
EFS - time from study entry until failure to achieve complete remission during consolidation, relapse, or death. For further clarification see definitions provided in the protocol.
次要结局
- Hematologic Remission Rate(End of consolidation, course 1: up to 5 months)
- Hematologic, Molecular, and Cytogenetic Remission Rate(End of consolidation, course 3; up to 7 months (for Standard Risk) or end of consolidation, course 4; up to 9 months (for High Risk))
- Overall Survival (OS)(At 3 years from study entry)