A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-Trans Retinoic Acid
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 158
- 试验地点
- 174
- 主要终点
- Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients
研究概览
简要总结
This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia. Standard treatment for acute promyelocytic leukemia involves high doses of a common class of chemotherapy drugs called anthracyclines, which are known to cause long-term side effects, especially to the heart. Tretinoin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Arsenic trioxide may stop the growth of cancer cells by either killing the cells, by stopping them from dividing, or by stopping them from spreading. Completely removing or reducing the amount of anthracycline chemotherapy and giving tretinoin together with arsenic trioxide may be an effective treatment for acute promyelocytic leukemia and may reduce some of the long-term side effects.
详细描述
PRIMARY OBJECTIVES:
I. To eliminate exposure to conventional chemotherapy (including anthracyclines), for patients with standard risk acute promyelocytic leukemia (APL), through use of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) (tretinoin) based therapy while achieving an event free survival (EFS) that is not inferior compared to historical controls.
II. To significantly reduce exposure to conventional chemotherapy, and in particular, anthracycline exposure, for patients with high risk APL, through use of ATO and ATRA based therapy while achieving an event free survival that is not inferior compared to historical controls.
EXPLORATORY OBJECTIVES:
I. To analyze the clinical impact of FMS-like tyrosine kinase 3 (FLT3) mutations in pediatric APL.
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
- 12 Months 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 APL (initially by morphology of 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
- •If the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate the PML-RARalpha transcript by RQ-PCR to be eligible
- •NOTE: A lumbar puncture is not required in order to be enrolled on study nor are lumbar punctures recommended at the time of diagnosis; if the diagnosis of APL is known or suspected, diagnostic lumbar punctures in patients with neurologic symptoms should be deferred until any coagulopathy is corrected; if central nervous system (CNS) disease is suspected or proven, a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma; if CNS disease is documented, patients are still eligible and will receive protocol directed intrathecal treatments
- •Patients may receive up to a maximum of 5 days of pre-treatment with ATRA prior to administration of protocol therapy
- •Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine prior to beginning protocol directed therapy is allowed; however, it should be noted that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not recommended
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Patients with secondary APL are excluded; this includes all patients with APL that may have resulted from prior treatment (chemotherapy or radiation)
- •Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) but without evidence of APL by bone marrow or peripheral blood morphology are excluded
- •Patients with a pre-existing diagnosis of a prolonged QT syndrome (even if corrected QT interval [QTc] is normal at the time of APL diagnosis) are excluded
- •Patients with a baseline QTc of > 450 msec are excluded; Bazett's formula is to be used for measurement of the corrected QT interval: the QT interval (msec) divided by the square root of the RR interval (msec)
- •Patients with a history or presence of significant ventricular or atrial tachyarrhythmia are excluded
- •Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded
- •Patients with serum creatinine > 3.0 mg/dL and patients on active dialysis for renal dysfunction are excluded
- •Patients who have received treatment with any other cytotoxic chemotherapy prior to beginning protocol therapy (other than allowed in above criteria) are excluded
- •Female patients who are pregnant are excluded; patients should not be pregnant or plan to become pregnant while on treatment; a pregnancy test prior to enrollment is required for female patients of childbearing potential
- •Lactating females who plan to breastfeed their infants are excluded
- •Sexually active patients of reproductive potential who have not agreed to be abstinent or use 2 forms of effective contraception during treatment through 1 month off therapy are excluded
研究组 & 干预措施
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Arsenic Trioxide (Drug)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Cytarabine (Drug)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Dexamethasone (Drug)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Idarubicin (Drug)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Mitoxantrone Hydrochloride (Drug)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Quality-of-Life Assessment (Other)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Treatment (tretinoin, arsenic trioxide, chemotherapy)
See Detailed Description
干预措施: Tretinoin (Drug)
结局指标
主要结局
Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients
时间窗: Up to 24 months
EFS is defined as the time from on study to failure to achieve hematological complete response (CR) prior to start of consolidation, persistence of molecular positive disease after minimal residual disease (MRD) positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits.
EFS in High Risk APL Patients
时间窗: Up to 24 months
EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits.
次要结局
未报告次要终点