B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021 (B-NHL-M-2021)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Event-free survival
研究概览
简要总结
The aim of the trial is to evaluate the molecular characteristics and MDD/MRD of B-NHL in pediatric patients in order to identify on the one hand the very high risk group and to prescribe them more intensive treatment on the other hand to identify those patients who don't need very aggressive therapy. One more study question is to evaluate the role of PET/CT in assessment of the completeness of remission.
The following primary study questions are going to be analyzed:
- the effectiveness (event-free survival) in pediatric patients with very limited mature B-NHL (R1 - stage I and II R) of substituting anthracyclines and vincristine by the rituximab without compromising survival rates.
- the effectiveness (event-free survival) in pediatric patients with limited mature B-NHL (R2 - stage I and II NR) of substituting anthracyclines by the rituximab without compromising survival rates.
- the effectiveness (event-free survival) in pediatric patients with advanced VHR mature B-NHL (R4 - stages with unfavourable genetics of substituting standard chemotherapy by "second-line" block VICI in order to improve results
Secondary study questions will address
- additional parameters for immune reconstitution, lymphocyte subpopulations, immunoglobulin levels, vaccination titers and infection rates
- kinetics of immune reconstitution after treatment
详细描述
Detailed Description:
Risk group stratification:
R1: resection status: complete, stage I and II R2: resection status: incomplete, stage I and II R3: resection status: incomplete, stage III and LDH < 2 x ULN R4: resection status: incomplete, stage III and LDH ≥ 2 x ULN, stage IV/B-AL and CNS negative; CNS +
For patients with very limited disease (R1- stage I/II СR), the addition of rituximab might allow the omission of anthracyclines and vincristine without jeopardizing survival rates but reducing acute and long term toxicities. In this treatment arm, it is tested whether the event-free survival is similar to that of the historical control For patients with limited disease (R2- stage I/II NR), the addition of rituximab might allow the omission of anthracyclines without jeopardizing survival rates but reducing acute and long term toxicities.
For patients with limited disease (R3 - stage III and LDH < 2 x ULN ), the addition of rituximab might allow reduce the number of blocks to four without jeopardizing survival rates but reducing toxicities For patients with obligate factors of poor prognosis (additional adverse cytogenetic findings (TP-53, 11qLOH) it is tested whether the event-free survival can be improved by adding rituximab and adding blocks R-VICI
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
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at diagnosis 0 to 18 years.
- •The diagnosis of Burkitt's lymphoma, Diffuse large B-cell lymphom, primary mediastinal lymphoma, primary CNS lymphoma, B-cell (Burkitt) AL
- •Informed consent of the patient parents (guardians) to be treated
排除标准
- •previous malignancy, prior organ transplant, HIV infection or AIDS or severe immunodeficiency
- •hypersensitivity to rituximab or to ingredients of other IMPs.
- •no informed consent of the patient parents (guardians) to be treated
研究组 & 干预措施
R1: stage I and II
R1: resection status: complete, stage I and II
干预措施: Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate (Drug)
R2: incomplete, stage I and II
R2: resection status: incomplete, stage I and II
干预措施: Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate, Vincristine (Drug)
R3: incomplete, stage III and LDH < 2 x ULN
R3: resection status: incomplete, stage III and LDH < 2 x ULN
干预措施: Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, vincristine (Drug)
R4: stage III and LDH ≥ 2 x ULN, stage IV/B-AL and CNS negative; CNS +
R4: resection status: incomplete, stage III and LDH ≥ 2 x ULN, stage IV/B-AL and CNS negative; CNS +
干预措施: Cyclophosphamide , Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, Vincristine, Сarboplatine, CCNU/ BCNU, Melphalan, Idarubicin (Drug)
结局指标
主要结局
Event-free survival
时间窗: 7 years after the start of therapy
Event-free survival The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.
次要结局
- assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol(7 years after the start of therapy)
- assessment of PET-CT results - initial and control points (early PET response).after the 2nd block(after the 2nd block - CT with CL of the involved areas, PET-CT examination on the 14th day (maximum on the 17th day) after the last injection of CT, IPT, MRD in the bone marrow - after 4th block - CT with the CL of the involved areas)
- assessment of PET-CT results - initial and control points (early PET response) after 4th block(PET-CT examination on the 14th day (maximum on the 17th day) after the last administration of CT, MRD in the bone marrow if present after the 2nd block)
- Relapse-free survival (RFS)(7 years after the start of therapy)
- Response rate (RR) [ and after second course and after two injections of rituximab]. Complete response, partial remission, stable disease or progressive disease(7 years after the start of therapy)
- Rate of patients achieving normal immunoglobulin level(12 months after start of treatment)
- Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment(12 months after start of treatment)
- Interval to normal lymphocyte subpopulations in the peripheral blood.(7 years after the start of therapy)
- Rate of patients with sufficient titers after vaccination one year after start of treatment(1 year after start of treatment)
- Immune reconstitution rate (only in R1/R2 patients)(1 year after start of treatment)
- Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood.(1 year after start of treatment)