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

Children's Cancer Group, China

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Mature B-cell Non-Hodgkin Lymphoma

Treatments: Drug: Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone; Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone; Drug: Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone; Drug: Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone; Drug: Prednisone,Vincristine, Cyclophosphamide; Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT07168980

CCCG-BNHL-2025

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 87 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Histology or cytologically confirmed matureB-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

Exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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87 participants in 4 patient groups

Risk group 1

Other group

Description:

Complete resection of stage I or II disease: 3 courses (A-B-A) and 3 intrathecal injections(Cytarabine/Methotrexate/Dexamethasone, age adjusted);

Treatment:

Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Drug: Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone

Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Risk group 2

Other group

Description:

Not or incompletely resected stage I/II disease and LDH \<2ULN: 5 courses (A--B--A--B--A) and 8 intrathecal injections;

Treatment:

Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone

Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Risk group 3

Other group

Description:

Stage III with LDH \< 2 ULN, or Stage I,II with LDH in 2 to 4 ULN : Preface followed by 6 courses (P(Cyclophosphamide/Vincristine/Prednisone)-AA-BB-AA-BB-AA-BB) and 13 intrathecal injections(16 intrathecal injections with CNS2-3)

Treatment:

Drug: Prednisone,Vincristine, Cyclophosphamide

Drug: Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone

Drug: Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone

Risk group 4

Other group

Description:

Stage III with LDH≥2ULN, or Stage IV, or B-AL: Preface followed by 6 dose of rituximab (375mg/m2) combined 6 courses of chemotherapy, together with 13 intrathecal injections((16 intrathecal injections with CNS2-3): P-(Rituximab-Rituximab)AA-(Rituximab-Rituximab)BB-(Rituximab)AA-(Rituximab)BB-AA-BB; stage IV or B-AL with LDH≥5ULN:P-(Rituximab-Rituximab)AA-(Rituximab-Rituximab)BB-(Rituximab)AA-(Rituximab)BB-AA-BB-AA-BB, together with 17 intrathecal injections((21 intrathecal injections with CNS2-3)

Treatment:

Drug: Prednisone,Vincristine, Cyclophosphamide

Drug: Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone

Drug: Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone