Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 28
- 主要终点
- AALL08P1 Safety Outcome
研究概览
简要总结
This pilot clinical trial studies the side effects of pegaspargase when given together with combination chemotherapy in treating patients with newly diagnosed high-risk acute lymphoblastic leukemia. Pegaspargase may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) together with pegaspargase may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation and ending with completion of delayed intensification (DI) in combination with hemi-augmented BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic leukemia (ALL).
OUTLINE: Patients are stratified according to risk assignment (high-risk [HR]-average [day 29 minimal residual disease (MRD) < 0.01%] vs HR-high [MRD >= 0.01%, presence of central nervous system [CNS]3 leukemia, testicular disease, myeloid/mixed lineage leukemia [MLL] rearrangement, hypodiploidy, or steroid therapy within the past month]). Patients are assigned to 1 of 2 treatment groups.*
(Note: *Amendment 2 [4-22-2011] requires changes in the regimens. See the changes below, after Maintenance therapy.)
INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT on days 8 and 29*; and pegaspargase IV over 1-2 hours on day 4.
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
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be eligible for and enrolled on AALL03B1 or the successor classification study
- •Patients must have newly diagnosed high-risk B-precursor acute lymphoblastic leukemia (ALL)
- •WBC criteria
- •Age 1.00-9.99 years: WBC >= 50,000/uL
- •Age 10.00 - 30.99 years: Any WBC
- •Prior steroid therapy: Any WBC
- •Patients with testicular leukemia: Any WBC
- •Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine
- •Intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment; systemic chemotherapy must begin within 72 hours of this intrathecal therapy
- •Patients receiving prior steroid therapy are eligible for study; the dose and duration of previous steroid therapy should be carefully documented
- •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
- •Pregnant female patients are ineligible; pregnancy tests with a negative result must be obtained in all post-menarchal females; males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; lactating females must agree that they will not breastfeed a child while on this study
- •Patients with Down syndrome (DS) are ineligible since excessive toxicities and death have been noted for those enrolled on AALL0232 receiving the prednisone/Capizzi methotrexate (PC) arm of treatment, which is the backbone regimen for the current study
研究组 & 干预措施
Arm I (HR-average)
See Detailed Description.
干预措施: Cyclophosphamide (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Cytarabine (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Dexamethasone (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (HR-average)
See Detailed Description.
干预措施: Mercaptopurine (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Methotrexate (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Pegaspargase (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Thioguanine (Drug)
Arm I (HR-average)
See Detailed Description.
干预措施: Vincristine Sulfate (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Cyclophosphamide (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Cytarabine (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Dexamethasone (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (HR-high)
See Detailed Description.
干预措施: Mercaptopurine (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Methotrexate (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Pegaspargase (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Prednisone (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Prophylactic Cranial Irradiation (Radiation)
Arm II (HR-high)
See Detailed Description.
干预措施: Thioguanine (Drug)
Arm II (HR-high)
See Detailed Description.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
AALL08P1 Safety Outcome
时间窗: Consolidation through Delayed Intensification
Percentage of Group B (High Risk-High) patients taking less than 49 weeks from day 1 of consolidation to day 1 of maintenance therapy. Only Group B analyzed since this is prespecified in protocol.
AALL08P1 Feasibility Outcome
时间窗: Consolidation through Delayed Intensification
Percentage of Group B (High Risk-High) patients that tolerate at least 8 of the 12-14 total doses of pegaspargase during Consolidation, Interim Maintenance, and Delayed Intensification periods. Only Grp B analyzed since this is prespecified in protocol.
次要结局
未报告次要终点