BNHL-2015 for Children or Adolescents in China

NCT ID: NCT02405676

Last Updated: 2025-02-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2029-12-31

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.

Conditions

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Mature B-cell Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Risk group 1

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

Group Type OTHER

Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Intervention Type DRUG

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;

Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone

Intervention Type DRUG

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;

Risk group2

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

Group Type OTHER

Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Intervention Type DRUG

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;

Ifosphamide, Etoposide, Methotrexate, Vincristine, Prednisone

Intervention Type DRUG

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;

Risk group3

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.

Group Type OTHER

Prednisone,Vincristine, Cyclophosphamide

Intervention Type DRUG

Prednisone 45mg/m2, D1\~7; Vincristine 1.5mg/m2(MAX 2mg), D1; Cyclophosphamide 300mg/m2, D1; Intrathecal injection, D1;

Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Intervention Type DRUG

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;

Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone

Intervention Type DRUG

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;

Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone

Intervention Type DRUG

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;

Risk group4

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.

Group Type OTHER

Prednisone,Vincristine, Cyclophosphamide

Intervention Type DRUG

Prednisone 45mg/m2, D1\~7; Vincristine 1.5mg/m2(MAX 2mg), D1; Cyclophosphamide 300mg/m2, D1; Intrathecal injection, D1;

Cyclophosphamide, Vincristine, Cytarabine, Doxorubincin, Prednisone

Intervention Type DRUG

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;

Cyclophosphamide, Vindelsine, Cytarabine, Doxorubincin, Prednisone

Intervention Type DRUG

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;

Ifosphamide, Etoposide, Methotrexate, Vindelsine, Prednisone

Intervention Type DRUG

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;

Rituximab

Intervention Type DRUG

375mg/m2, 4 injections for patients in Risk group4; D0 of Protocol AA or BB;

Interventions

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Prednisone,Vincristine, Cyclophosphamide

Prednisone 45mg/m2, D1\~7; Vincristine 1.5mg/m2(MAX 2mg), D1; Cyclophosphamide 300mg/m2, D1; Intrathecal injection, D1;

Intervention Type DRUG

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;

Intervention Type 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;

Intervention Type DRUG

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, D1,8;

Intervention Type DRUG

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;

Intervention Type DRUG

Rituximab

375mg/m2, 4 injections for patients in Risk group4; D0 of Protocol AA or BB;

Intervention Type DRUG

Other Intervention Names

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Preface Protocol A Protocol B Protocol AA Protocol BB

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.


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

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tongji Hospital

OTHER

Sponsor Role collaborator

Nanjing Children's Hospital

OTHER

Sponsor Role collaborator

West China Second University Hospital

OTHER

Sponsor Role collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role collaborator

Children's Hospital of Soochow University

OTHER

Sponsor Role collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role collaborator

Children's Cancer Group, China

NETWORK

Sponsor Role lead

Responsible Party

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Yi-Jin Gao

Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yi-Jin Gao, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Children's Medical Center

Locations

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West China Second University Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status

Countries

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China

References

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Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, Mann G, Chott A, Ebell W, Klingebiel T, Graf N, Kremens B, Muller-Weihrich S, Pluss HJ, Zintl F, Henze G, Riehm H. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood. 1999 Nov 15;94(10):3294-306.

Reference Type BACKGROUND
PMID: 10552938 (View on PubMed)

Miles RR, Arnold S, Cairo MS. Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia. Br J Haematol. 2012 Mar;156(6):730-43. doi: 10.1111/j.1365-2141.2011.09024.x. Epub 2012 Jan 20.

Reference Type BACKGROUND
PMID: 22260323 (View on PubMed)

Woessmann W, Seidemann K, Mann G, Zimmermann M, Burkhardt B, Oschlies I, Ludwig WD, Klingebiel T, Graf N, Gruhn B, Juergens H, Niggli F, Parwaresch R, Gadner H, Riehm H, Schrappe M, Reiter A; BFM Group. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Blood. 2005 Feb 1;105(3):948-58. doi: 10.1182/blood-2004-03-0973. Epub 2004 Oct 14.

Reference Type BACKGROUND
PMID: 15486066 (View on PubMed)

Meinhardt A, Burkhardt B, Zimmermann M, Borkhardt A, Kontny U, Klingebiel T, Berthold F, Janka-Schaub G, Klein C, Kabickova E, Klapper W, Attarbaschi A, Schrappe M, Reiter A; Berlin-Frankfurt-Munster group. Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia. J Clin Oncol. 2010 Jul 1;28(19):3115-21. doi: 10.1200/JCO.2009.26.6791. Epub 2010 Jun 1.

Reference Type BACKGROUND
PMID: 20516455 (View on PubMed)

Goldman S, Smith L, Anderson JR, Perkins S, Harrison L, Geyer MB, Gross TG, Weinstein H, Bergeron S, Shiramizu B, Sanger W, Barth M, Zhi J, Cairo MS. Rituximab and FAB/LMB 96 chemotherapy in children with Stage III/IV B-cell non-Hodgkin lymphoma: a Children's Oncology Group report. Leukemia. 2013 Apr;27(5):1174-7. doi: 10.1038/leu.2012.255. Epub 2012 Sep 3. No abstract available.

Reference Type BACKGROUND
PMID: 22940833 (View on PubMed)

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: 10.1007/s00277-022-04904-w. Epub 2022 Jul 13.

Reference Type DERIVED
PMID: 35829780 (View on PubMed)

Other Identifiers

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CCCG-BNHL-2015

Identifier Type: -

Identifier Source: org_study_id

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