A Phase III Study of Large Cell Lymphomas in Children and Adolescents: Comparison of APO vs APO + IDMTX/HDARA-C and Continuous vs Bolus Infusion of Doxorubicin
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 242
- 试验地点
- 10
- 主要终点
- Event free survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different doses may kill more cancer cells.
PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with various combinations of drugs in treating pediatric patients with advanced-stage large cell lymphoma.
详细描述
OBJECTIVES: I. Compare the event free survival of children with advanced stage large cell lymphoma treated with modified APO (doxorubicin/prednisone/vincristine/mercaptopurine) with or without intermediate-dose methotrexate/high dose cytarabine as maintenance therapy following induction therapy with APO. II. Characterize further the immunophenotypic and morphologic correlates of pediatric large cell lymphoma.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms, except for those with CNS disease. These patients are assigned to arm II and receive whole brain irradiation on Regimen B. Arm I: Induction (Modified APO): Patients receive vincristine IV on days 1, 8, 15, 22, and 29, doxorubicin IV over 15 minutes on days 1 and 22, prednisone three times a day on days 1-28, and methotrexate intrathecally (IT) on days 1, 8, and 22. Patients in complete remission on day 43 proceed to maintenance, those in partial remission undergo biopsy then proceed to maintenance, and those with residual disease receive radiotherapy on regimen A concurrently with maintenance. Maintenance (day 1 is day 43 of Induction): Courses of intermediate dose methotrexate/leucovorin calcium and high dose cytarabine (ID MTX/CF/HD ARA-C) and modified APO alternate every 3 weeks. Patients receive a total of 15 courses (8 of ID MTX/CF/HD ARA-C and 7 of Modified APO). ID MTX/CF/HD ARA-C: Patients receive methotrexate IV over 24 hours on day 1, leucovorin calcium IV or orally every 6 hours on days 2 and 3, cytarabine IV over 48 hours on days 2 to 4, and methotrexate IT on day 1 of courses 1, 3, and 5. Filgrastim (G-CSF) is administered beginning on day 5 and continuing until blood counts recover. Modified APO: Patients receive vincristine IV on day 1, oral mercaptopurine on days 1-5, doxorubicin IV over 15 minutes on day 1, and oral prednisone three times a day on days 1-5. Arm II: Induction: Patients receive treatment as in arm I except that patients with CNS disease also receive methotrexate IT on days 15, 29, and 36. Maintenance (day 1 is day 43 of Induction): Modified APO: as in Arm I, with methotrexate administered on day 1 of courses 1, 3, and 5 (days 1-5 for patients with CNS disease). Courses repeat every 21 days for a total of 15 courses. Patients with CNS disease begin radiotherapy on Regimen B on week 2 of maintenance. Regimen A: Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance. Regimen B: Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
PROJECTED ACCRUAL: A total of 242 patients will be accrued for this study over approximately 5.4 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
入排标准
- 年龄范围
- — 至 21 Years（Child, 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
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: filgrastim (Biological)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: cytarabine (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: doxorubicin hydrochloride (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: leucovorin calcium (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: mercaptopurine (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: methotrexate (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: prednisone (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: vincristine sulfate (Drug)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: low-LET cobalt-60 gamma ray therapy (Radiation)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: low-LET electron therapy (Radiation)
Regimen A
Patients begin radiotherapy (5 days a week for 4.5 weeks) to residual tumor on day 1 of maintenance.
干预措施: low-LET photon therapy (Radiation)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: filgrastim (Biological)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: cytarabine (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: doxorubicin hydrochloride (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: leucovorin calcium (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: mercaptopurine (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: methotrexate (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: prednisone (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: vincristine sulfate (Drug)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: low-LET cobalt-60 gamma ray therapy (Radiation)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: low-LET electron therapy (Radiation)
Regimen B
Patients receive whole brain irradiation (5 days a week for 3.1 weeks) beginning on day 1 of maintenance. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 3 years, and annually thereafter.
干预措施: low-LET photon therapy (Radiation)
结局指标
主要结局
Event free survival
时间窗: Length of study
To study whether intermediate-dose methotrexate/high-dose Ara-C (ID MTX/HDAra-C), administered during the maintenance phase can improve the event free survival (EFS) of patients with advanced-stage large cell lymphoma (LCL).
次要结局
未报告次要终点