Intergroup Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Evaluation of Rituximab Efficacy and Safety in High Risk Patients - Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 482
- 试验地点
- 10
- 主要终点
- Event free survival
研究概览
简要总结
The aim of the trial is to test whether adding 6 injections of rituximab to standard "Lymphome malin B" LMB chemotherapy regimen improves the Event Free Survival (EFS) compared with LMB chemotherapy alone in children / adolescents with advanced stage B-cell Non-Hodgkin Lymphoma (NHL) / B-Acute Leukemia (B-AL)(stage III and LDH > Nx2, any stage IV or B-AL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically proven B-cell malignancies, either Burkitt lymphoma or B-AL (=Burkitt leukaemia = L3-AL) or diffuse large B-cell NHL or aggressive mature B-cell NHL non other specified or specifiable.
- •Stage III with elevated LDH level ("B-high"), [LDH > twice the institutional upper limit of the adult normal values (> Nx2)] or any stage IV or B-AL.
- •6 months to less than 18 years of age at the time of consent.
- •Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab and during five months for men, taking into account the characteristics of methotrexate.
- •Complete initial work-up within 8 days prior to treatment that allows definite staging.
- •Able to comply with scheduled follow-up and with management of toxicity.
- •Signed informed consent from patients and/or their parents or legal guardians
排除标准
- •Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study
- •Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology.
- •Evidence of pregnancy or lactation period.
- •There will be no exclusion criteria based on organ function.
- •Past or current anti-cancer treatment except corticosteroids during less than one week.
- •Tumor cell negative for CD20
- •Prior exposure to rituximab.
- •Severe active viral infection, especially hepatitis B.
- •Hepatitis B carrier status history of HBV or positive serology.
- •Participation in another investigational drug clinical trial.
- •Patients who, for any reason, are not able to comply with the national legislation.
研究组 & 干预措施
LMB chemo
Prephase (COP) for all groups followed by:
- in group B: 4 courses: 2 COPADM + 2 CYM, with MTX 3g/m²
- in group C: 6 courses: 2 COPADM + 2 CYVE + 2 maintenance courses, with MTX 8g/m², in 4h in C1, in 24h in C3 (except the 1st course) and CNS positive patients receive additional IT before each CYVE courses and HDMTX between CYVE courses.
干预措施: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C (Drug)
LMB chemo + Rituximab
LMB chemo as in the comparator arm Rituximab 375 mg/m² i.v.: 6 injections: two doses at 48h interval are given at D-2 and D1 of the 2 first courses (COPADM) and one dose at the beginning of the 2 following courses (CYM or CYVE).
干预措施: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C (Drug)
结局指标
主要结局
Event free survival
时间窗: 24 months
Minimum time to death from any cause, presence of viable cells in residue after \[2nd (Rituximab-)CYVE\], relapse, progressive disease, or second malignancy measured from randomization.
次要结局
- Survival(5 years)
- Acute toxicity(6 months)
- Long term toxicity(5 years)