BNHL-2015 for Children or Adolescents in China

Study Overview
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Brief Summary
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The purpose of this study is to test whether adding 4 injections of rituximab and increasing the intensity of chemotherapy regimens in advanced patients can improve the EFS compared with the historical study CCCG-NHL-2010.

Detailed Description
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In our previous study (CCCG-NHL-2010), two-year EFS was 100% for Stage I, 91.3% ± 6.1% for Stage II, 75.8% ± 4.4% for Stage III, 56.3% ± 13.5% for Stage IV, and 36.4% ± 14.5% for B-AL, respectively. To improve survival for pediatric patients with B-NHL/B-AL, the investigators launched a new study in China. Compared with our previous treatment regimens (CCCG-2010), patients with stage III and LDH>4 times NL, any stage IV or B-AL were stratified into R4. The dose of methotrexate was increased to 5000mg/m2 for patients in R3 or R4 (previously 3000mg/m2). Four injections of rituximab was added to the chemotherapy for patients in R4. Our aim is to test whether adding rituximab or high dose of methotrexate (5000mg/m2) would improving 2-year EFS for patients in advanced groups.

Official Title
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Treatment Regimen or Children or Adolescent With Mature B-cell NHL or B-AL in China

Conditions
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Mature B-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Prednisone,Vincristine, Cyclophosphamide
* Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone
* Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone
* Drug: Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone
* Drug: Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Risk group 1<br>Complete resection of stage I or II disease: 3 courses (A-B-A) and 3 intrathecal injections(Cytarabine/Methotrexate/Dexamethasone, age adjusted); | Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone<br>* 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;<br>* Other names: Protocol A;Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone<br>* 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;<br>* Other names: Protocol B;|
| Other: Risk group2<br>Not or incompletely resected stage I/II disease and LDH <2 times NL: 5 courses (A--B--A--B--A) and 8 intrathecal injections; | Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone<br>* 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;<br>* Other names: Protocol A;Drug: Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone<br>* 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;<br>* Other names: Protocol B;|
| Other: Risk group3<br>Stage III with high LDH < 4 times NL, or Stage I,II with LDH >=2 times NL: Preface followed by 6 courses (P(Cyclophosphamide/Vincristine/Prednisone)-A-BB-AA-BB-AA-BB) and 13 intrathecal injections; Dosage of Cytarabine, Methotrexate and Etoposide was increased in AA or BB compared with A or B. Vindelsine was used in AA/BB instead of Vincristine in A/B. | Drug: Prednisone,Vincristine, Cyclophosphamide<br>* Prednisone 45mg/m2, D1 7; Vincristine 1.5mg/m2(MAX 2mg), D1; Cyclophosphamide 300mg/m2, D1; Intrathecal injection, D1;<br>* Other names: Preface;Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone<br>* 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;<br>* Other names: Protocol A;Drug: Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone<br>* 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, D1,8;<br>* Other names: Protocol AA;Drug: Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone<br>* 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;<br>* Other names: Protocol BB;|
| Other: Risk group4<br>Stage III with LDH≥4N, or Stage IV, or B-AL: Preface followed by 4 dose of rituximab (375mg/m2) combined 6 courses of chemotherapy, together with 13 intrathecal injections: P-A-(Rituximab)BB-(Rituximab)AA-(Rituximab)BB-(Rituximab)AA-BB; rituximab is at D0 of each course. | Drug: Prednisone,Vincristine, Cyclophosphamide<br>* Prednisone 45mg/m2, D1 7; Vincristine 1.5mg/m2(MAX 2mg), D1; Cyclophosphamide 300mg/m2, D1; Intrathecal injection, D1;<br>* Other names: Preface;Drug: Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone<br>* 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;<br>* Other names: Protocol A;Drug: Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone<br>* 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, D1,8;<br>* Other names: Protocol AA;Drug: Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone<br>* 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;<br>* Other names: Protocol BB;Drug: Rituximab<br>* 375mg/m2, 4 injections for patients in Risk group4; D0 of Protocol AA or BB;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival |  | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, non-Hodgkin, B-lymphocytes, Child, Multicenter study