Chemotherapy With Rituximab for Aggressive B-NHL in Children and Adolescents

Официальное название

Intensive Chemotherapy Combined With Early, Adequate, and Intensive Use of Rituximab for Aggressive B-NHL in Children and Adolescents

Обзор

The purpose of this study is to test whether intensive chemotherapy combined with early, adequate, and intensive use of Rituximab for aggressive B-NHL in children and adolescents can improve the EFS and OS compared with the historical study CCCG-BNHL-2015.

Подробное описание

In our previous study (CCCG-BNHL-2015), four-year EFS was 88.3%, mostly owing to the use of Rituximab. However, four-year EFS was only 73% for group R4. And three-year EFS was even lower, 61% for stage IV and B-AL with LDH≥4ULN. To improve survival for pediatric patients with high risk B-NHL, the investigators launched a new study in China. In this study (CCCG-BNHL-2025), patients with stage III and LDH≥2ULN, any stage IV, and B-AL will be stratified into group R4. Six injections of Rituximab will be used for patients in R4, compared with four injections in CCCG-BNHL-2015. And two injections of Rituximab will be used in the first and second cycles of chemotherapies. The first cycle of chemotherapy will be changed into AA, instead of A. For patients with stage IV (including B-AL) with LDH≥ 4ULN, two cycles of chemotherapies(AA and BB) will be added. Our aim is to test whether intensive chemotherapies with early, adequate, and intensive use of Rituximab will improve the EFS and OS of children and adolescents with highly aggressive B-NHL.

Вмешательства

• Препарат Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone
  Cyclophosphamide 800mg/m2, D1, then 200mg/m2, D2\~4;Vincristine 1.5mg/m2 (MAX 2mg), D1; Cytarabine 1g/m2/dose, (2 doses, 12-hour interval), D4; Doxorubincin 20mg/m2, D2,3; Prednisone 60mg/m2, D1\~7;Intrathecal injection, D1;
• Препарат Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone
  Ifosphamide 1.2g/m2, D1\~5; Etoposide, 60mg/m2, D3\~5; Methotrexate, 0.5g/m2, D1;Vincristine 1.5mg/m2 (MAX 2mg), D1; Prednisone 60mg/m2, D1\~7;Intrathecal injection, D1;
• Препарат Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone
  Cyclophosphamide 800mg/m2, D1, then 200mg/m2, D2\~4;Vincristine 1.5mg/m2 (MAX 2mg), D1; Cytarabine 1g/m2/dose, (2 doses, 12-hour interval), D4;Doxorubincin 20mg/m2, D2,3; Prednisone 60mg/m2, D1\~7;Intrathecal injection, D1,8;
• Препарат Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone
  Ifosphamide 1.2g/m2, D1\~5; Etoposide, 60mg/m2, D3\~5; Methotrexate, 0.5g/m2, D1;Vincristine 1.5mg/m2 (MAX 2mg), D1; Prednisone 60mg/m2, D1\~7;Intrathecal injection, D1
• Препарат Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone
  Cyclophosphamide 800mg/m2, D1, then 200mg/m2, D2\~4; Vindelsine 3mg/m2 (MAX 5mg), D1; Cytarabine 2g/m2/dose, (2 doses, 12-hour interval), D4; Doxorubincin 20mg/m2, D2,3; Prednisone 60mg/m2, D1\~7;Intrathecal injection, D1,4(CNS2-3),8
• Препарат Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone
  Ifosphamide 1.2g/m2, D1\~5; Etoposide, 100mg/m2, D3\~5; Methotrexate, 5g/m2, D1;Vindelsine 3mg/m2 (MAX 5mg), D1; Prednisone 60mg/m2, D1\~7;Intrathecal injection, D1,8
• Препарат Prednisone,Vincristine, Cyclophosphamide
  Prednisone 45mg/m2, D1\~7; Vincristine 1.5mg/m2(MAX 2mg), D1; Cyclophosphamide 300mg/m2, D1; Intrathecal injection, D1

Первичные конечные точки

• Event free survival [Срок оценки: 3 years]

Вторичные конечные точки (1)

• Overall survival [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Histology or cytologically confirmed mature B-cell NHL/AL(Burkitt, DLBCL, PMLBL,or aggressive mature B-cell NHL non other specified or specifiable)
• Able to comply with scheduled follow-up and with management of toxicity
• Signed informed consent

Критерии исключения

• 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. Past or current anti-cancer treatment except corticosteroids during less than one week.

Exclusion Criteria related to Rituximab :

• Tumor cell negative for CD20
• Prior exposure to rituximab
• Hepatitis B carrier status history of HBV or positive serology.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Children's Medical Center — Шанхай

Публикации

• Dong J, Xu Z, Guo X, Ye F, Fan C, Gao J, Gao Y, Yang L. Effect of rituximab on immune status in children with aggressive mature B-cell lymphoma/leukemia-a prospective study from CCCG-BNHL-2015. Heliyon. 2024 Mar 5;10(5):e27305. doi: 10.1016/j.heliyon.2024.e27305. eCollection 2024 Mar 15. PMID 38495131
• Zhao J, Liu TF, Wu KF, Yang LC, Xu XJ, Lu J, Shao JB, Li F, Ma FT, Guo X, Li H, Liu AG, Wang NL, Shen HP, Li Y, Liu SX, Liang CD, Shen SH, Fang YJ, Gao YJ. Clinical and molecular characteristics of paediatric mature B-cell acute lymphocytic leukaemia and non-Hodgkin lymphoma with bone marrow involvement: A joint study between the CCCG leukaemia and lymphoma groups. Br J Haematol. 2025 Apr;206(4):1 PMID 39962993
• Wang X, Ding L, Fang Y, Yan J, Gao J, Yang L, Liu A, Lu J, Wang J, Zhang A, Gao Y, Ju X. The Prognostic and Risk Factors for Children With High-Risk Mature B-Cell Non-Hodgkin's Lymphoma: A Retrospective Multicenter Study. Cancer Med. 2024 Nov;13(21):e70309. doi: 10.1002/cam4.70309. PMID 39513286
• Minard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children's Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Eng PMID 32492302
• Gao YJ, Fang YJ, Gao J, Yan J, Yang LC, Liu AG, Ju XL, Lu J, Han YL, Wang J, Xie M, Guo X, Tang JY. A prospective multicenter study investigating rituximab combined with intensive chemotherapy in newly diagnosed pediatric patients with aggressive mature B cell non-Hodgkin lymphoma (CCCG-BNHL-2015): a report from the Chinese Children's Cancer Group. Ann Hematol. 2022 Sep;101(9):2035-2043. doi: 10.1 PMID 35829780

Идентификаторы

NCT: NCT07168980 · CCCG-BNHL-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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