LBL-2016 for Children or Adolescents in China

NCT ID: NCT02845882

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2031-12-31

Brief Summary

The outcomes of children with lymphoblastic lymphoma (LBL) in China in the investigators' previous study were not unexpected. In this study, through further modification treatment protocols and strengthen domestic multicenter collaboration, the investigators try to improve survival for children with LBL when compared to the previous study.

Detailed Description

The treatment for LBL is an ALL (acute lymphoblastic leukemia)-based treatment. Additional, high dose L-asparaginase was reported to improve disease-free survival for patients with ALL. The event free survival (EFS) for pediatric LBL in most western countries have achieved 75% to 85%. However, the outcomes of children with LBL in China were not unexpected. In the previous study (CCCG-LBL-2010, 2009-2013), 96 patients with newly diagnosed LBL from 7 Chinese pediatric oncology centers were included. At a median follow-up of 21 months (range, 0.3~60.7months), the 2-year event free survival was 68±5% in all patients. Patients who had achieved complete remission on day 33 of induction had significantly better EFS than those who had not (77±6% v.s.17±10%, p<0.005). In the current trial, the investigators try to improve survival for children with LBL in China through further modification treatment protocols and strengthen domestic multicenter collaboration.

The BFM backbone will be used as the standard backbone therapy for this study. Three doses of daunorubicin are prescribed in induction compared with 4 doses in BFM studies. Cranial radiotherapy only saved for patients (>2 yrs) with CNS disease at presentation.

Complete remission (CR) is defined as at least 75% tumor regression, less than 5% BM (bone marrow)blasts, no CNS (central nervous system) disease, and disappearances of all evidence of disease from all sites for at least 4 weeks. Partial response (PR) is defined as > 50% tumor regression, and no new lesions.Response to treatment is evaluated on day 33 and day 64 of induction.Patients will be stratified into 3 risk groups.

Low risk group: patients (stage I or II) receive induction protocol I followed by the extracompartmental protocol M, and maintenance for up to a total therapy duration of 96 weeks. Totally, 3 doses of PEG-asparaginase (Pegylated-asparaginase) are applied in this group.

Intermediate risk group: patients (stage III or IV or receiving steroids within one week prior to the diagnosis) receive induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance for up to a total therapy duration of 104 weeks.Totally, 5 doses of PEG-asparaginase are applied in this group.

High risk group:patients (failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction) receive induction protocol I followed by 6 intensive polychemotherapy blocks (R'), reintensification protocol II, and maintenance for up to a total therapy duration of 104 weeks. Totally, 11 doses of PEG-asparaginase are applied in this group.

Second look biopsy/resection is indicated for patients without CR on day 64 of induction. Allo- or auto-hematopoietic stem-cell transplantation is recommended for patients with residual tumor. Patients who have disease progression at any time will be removed from this protocol therapy.

Conditions

Lymphoblastic Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low risk group

Stage I or II: Induction I followed by extracompartmental Protocol M, and maintenance therapy for up to a total therapy duration of 96 weeks. Twenty triple intrathecal injections.

Group Type: OTHER

Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Intervention Type: DRUG

Prednisone 60 mg/m2 per day,d1-28, then taper over 9 days; Vincristine 1.5 mg/m2 per day (max 2 mg),d1,8, 15, 22; Daunorubicin 30 mg/m2 per dose,d5,12,19; Pegylated-asparaginase 2000 IU/m2 per dose,d16,36,57; Cyclophosphamide 1000 mg/m2 per dose, d36, 57; Cytarabine 75 mg/m2 /d, d36-42,d 57-63; 6-Mercaptopurine 60 mg/m2 per day, d36-42, 57-63; Triple it, d8,29,36,57 1,8, 15, 22

6-mercaptopurine,Methotrexate

Intervention Type: DRUG

6-Mercaptopurine 25 mg/m2 per day, d1-56; Methotrexate 5g/m2 per dose, d1, 15, 29, 43; Triple it, d1, 15, 29, 43;

Methotrexate, 6-mercaptopurine

Intervention Type: DRUG

6-mercaptopurine 50 mg/m2 per day, Daily; Methotrexate 20 mg/m2 per dose, Once a week; Triple it, Once every 4 weeks for 12 times;

Intermediate risk group

Stage III or IV or receiving steroids within one week prior to the diagnosis: Induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.

Group Type: OTHER

Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Intervention Type: DRUG

Prednisone 60 mg/m2 per day,d1-28, then taper over 9 days; Vincristine 1.5 mg/m2 per day (max 2 mg),d1,8, 15, 22; Daunorubicin 30 mg/m2 per dose,d5,12,19; Pegylated-asparaginase 2000 IU/m2 per dose,d16,36,57; Cyclophosphamide 1000 mg/m2 per dose, d36, 57; Cytarabine 75 mg/m2 /d, d36-42,d 57-63; 6-Mercaptopurine 60 mg/m2 per day, d36-42, 57-63; Triple it, d8,29,36,57 1,8, 15, 22

6-mercaptopurine,Methotrexate

Intervention Type: DRUG

6-Mercaptopurine 25 mg/m2 per day, d1-56; Methotrexate 5g/m2 per dose, d1, 15, 29, 43; Triple it, d1, 15, 29, 43;

Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine

Intervention Type: DRUG

Dexamethasone 10 mg/m2 per day, d1-7, d15-21; Vincristine 1.5 mg/m2 per day (max 2 mg), d1, 8, 15; Doxorubicin 30 mg/m2 per dose, d1, 8, 15; Pegylated-asparaginase 2,000 IU/m2 per dose, d3, 24; Cyclophosphamide 1000 mg/m2 per dose, d29; Cytarabine 75 mg/m2 /d, d29-35; 6-Mercaptopurine 60 mg/m2 per day, d29-35; Triple it, d1, 29;

Methotrexate, 6-mercaptopurine

Intervention Type: DRUG

6-mercaptopurine 50 mg/m2 per day, Daily; Methotrexate 20 mg/m2 per dose, Once a week; Triple it, Once every 4 weeks for 12 times;

High risk group

Failure to qualify a PR, or \>5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.

Group Type: OTHER

Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Intervention Type: DRUG

Prednisone 60 mg/m2 per day,d1-28, then taper over 9 days; Vincristine 1.5 mg/m2 per day (max 2 mg),d1,8, 15, 22; Daunorubicin 30 mg/m2 per dose,d5,12,19; Pegylated-asparaginase 2000 IU/m2 per dose,d16,36,57; Cyclophosphamide 1000 mg/m2 per dose, d36, 57; Cytarabine 75 mg/m2 /d, d36-42,d 57-63; 6-Mercaptopurine 60 mg/m2 per day, d36-42, 57-63; Triple it, d8,29,36,57 1,8, 15, 22

Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine

Intervention Type: DRUG

Dexamethasone 10 mg/m2 per day, d1-7, d15-21; Vincristine 1.5 mg/m2 per day (max 2 mg), d1, 8, 15; Doxorubicin 30 mg/m2 per dose, d1, 8, 15; Pegylated-asparaginase 2,000 IU/m2 per dose, d3, 24; Cyclophosphamide 1000 mg/m2 per dose, d29; Cytarabine 75 mg/m2 /d, d29-35; 6-Mercaptopurine 60 mg/m2 per day, d29-35; Triple it, d1, 29;

Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Methotrexate

Intervention Type: DRUG

Dexamethasone 20mg/m2/day, d1-5; Vincristine 1.5 mg/m2 per day (max 2 mg), d1, 6; Methotrexate 5000mg/m2, d1; Cyclophosphamide 200mg/m2/dose, q12h×5, d2-4; Cytarabine 2000mg/m2/dose, ，q12h×2, d5; Pegylated-asparaginase 2,000 IU/m2 per dose, d6; Triple it, d1;

Dexamethasone, Vindesine, Methotrexate, Ifosfamide, Daunorubicin, Pegylated-asparaginase

Intervention Type: DRUG

Dexamethasone 20mg/m2/day, d1-5; Vindesine 3mg/m2（MAX 5mg）, d1, 6; Methotrexate 5000mg/m2, d1; Ifosfamide 800mg/m2/dose, q12h×5,d2-4; Daunorubicin 25mg/m2/dose, d5; Pegylated-asparaginase 2,000 IU/m2 per dose, d6; Triple it, d1;

Dexamethasone, Cytarabine, Etoposide, Pegylated-asparaginase

Intervention Type: DRUG

Dexamethasone 20mg/m2/day, d1-5; Cytarabine 2000mg/m2/dose，q12h× 4, d1, 2; Etoposide 100mg/m2/dose，q12h×5, d3,4,5; Pegylated-asparaginase 2,000 IU/m2 per dose, d6; Triple it, d5;

Methotrexate, 6-mercaptopurine

Intervention Type: DRUG

6-mercaptopurine 50 mg/m2 per day, Daily; Methotrexate 20 mg/m2 per dose, Once a week; Triple it, Once every 4 weeks for 12 times;

Interventions

Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Prednisone 60 mg/m2 per day,d1-28, then taper over 9 days; Vincristine 1.5 mg/m2 per day (max 2 mg),d1,8, 15, 22; Daunorubicin 30 mg/m2 per dose,d5,12,19; Pegylated-asparaginase 2000 IU/m2 per dose,d16,36,57; Cyclophosphamide 1000 mg/m2 per dose, d36, 57; Cytarabine 75 mg/m2 /d, d36-42,d 57-63; 6-Mercaptopurine 60 mg/m2 per day, d36-42, 57-63; Triple it, d8,29,36,57 1,8, 15, 22

Intervention Type: DRUG

6-mercaptopurine,Methotrexate

6-Mercaptopurine 25 mg/m2 per day, d1-56; Methotrexate 5g/m2 per dose, d1, 15, 29, 43; Triple it, d1, 15, 29, 43;

Intervention Type: DRUG

Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine

Dexamethasone 10 mg/m2 per day, d1-7, d15-21; Vincristine 1.5 mg/m2 per day (max 2 mg), d1, 8, 15; Doxorubicin 30 mg/m2 per dose, d1, 8, 15; Pegylated-asparaginase 2,000 IU/m2 per dose, d3, 24; Cyclophosphamide 1000 mg/m2 per dose, d29; Cytarabine 75 mg/m2 /d, d29-35; 6-Mercaptopurine 60 mg/m2 per day, d29-35; Triple it, d1, 29;

Intervention Type: DRUG

Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Methotrexate

Dexamethasone 20mg/m2/day, d1-5; Vincristine 1.5 mg/m2 per day (max 2 mg), d1, 6; Methotrexate 5000mg/m2, d1; Cyclophosphamide 200mg/m2/dose, q12h×5, d2-4; Cytarabine 2000mg/m2/dose, ，q12h×2, d5; Pegylated-asparaginase 2,000 IU/m2 per dose, d6; Triple it, d1;

Intervention Type: DRUG

Dexamethasone, Vindesine, Methotrexate, Ifosfamide, Daunorubicin, Pegylated-asparaginase

Dexamethasone 20mg/m2/day, d1-5; Vindesine 3mg/m2（MAX 5mg）, d1, 6; Methotrexate 5000mg/m2, d1; Ifosfamide 800mg/m2/dose, q12h×5,d2-4; Daunorubicin 25mg/m2/dose, d5; Pegylated-asparaginase 2,000 IU/m2 per dose, d6; Triple it, d1;

Intervention Type: DRUG

Dexamethasone, Cytarabine, Etoposide, Pegylated-asparaginase

Dexamethasone 20mg/m2/day, d1-5; Cytarabine 2000mg/m2/dose，q12h× 4, d1, 2; Etoposide 100mg/m2/dose，q12h×5, d3,4,5; Pegylated-asparaginase 2,000 IU/m2 per dose, d6; Triple it, d5;

Intervention Type: DRUG

Methotrexate, 6-mercaptopurine

6-mercaptopurine 50 mg/m2 per day, Daily; Methotrexate 20 mg/m2 per dose, Once a week; Triple it, Once every 4 weeks for 12 times;

Intervention Type: DRUG

Other Intervention Names

Induction I; Protocol M; Reinduction II; HR 1'; HR 2'; HR 3'; maintenance therapy

Eligibility Criteria

Inclusion Criteria

• Patients must have newly diagnosed lymphoblastic lymphoma; Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids (<420mg/m2)

Exclusion Criteria

• Patients with Down syndrome;
• Morphologically unclassifiable lymphoma
• 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.
• Ph+ lymphoblastic lymphoma

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Children's Medical Center

OTHER

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: collaborator

West China Second University Hospital

OTHER

Sponsor Role: collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role: collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Soochow University

OTHER

Sponsor Role: collaborator

Nanjing Children's Hospital

OTHER

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

Children's Cancer Group, China

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yi-Jin Gao, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shanghai Children's Medical Center

Locations

West China Second University Hospital

Chengdu, , China

Shanghai Children's Medical Center

Shanghai, , China

Countries

China

References

Burkhardt B, Reiter A, Landmann E, Lang P, Lassay L, Dickerhoff R, Lakomek M, Henze G, von Stackelberg A. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group. J Clin Oncol. 2009 Jul 10;27(20):3363-9. doi: 10.1200/JCO.2008.19.3367. Epub 2009 May 11.

Reference Type: RESULT

PMID: 19433688 (View on PubMed)

Reiter A, Schrappe M, Ludwig WD, Tiemann M, Parwaresch R, Zimmermann M, Schirg E, Henze G, Schellong G, Gadner H, Riehm H. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood. 2000 Jan 15;95(2):416-21.

Reference Type: RESULT

PMID: 10627444 (View on PubMed)

Moghrabi A, Levy DE, Asselin B, Barr R, Clavell L, Hurwitz C, Samson Y, Schorin M, Dalton VK, Lipshultz SE, Neuberg DS, Gelber RD, Cohen HJ, Sallan SE, Silverman LB. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Blood. 2007 Feb 1;109(3):896-904. doi: 10.1182/blood-2006-06-027714. Epub 2006 Sep 26.

Reference Type: RESULT

PMID: 17003366 (View on PubMed)

Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, Konja J, Kaiserova E, Kowalczyk J, Kovacs G, Li CK, Magyarosy E, Popa A, Stark B, Jabali Y, Trka J, Hrusak O, Riehm H, Masera G, Schrappe M. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014 Jan 20;32(3):174-84. doi: 10.1200/JCO.2013.48.6522. Epub 2013 Dec 16.

Reference Type: RESULT

PMID: 24344215 (View on PubMed)

Lymphoma Study Group, Subspecialty Group of Hematology, the Society of Pediatrics, Chinese Medical Association; Lymphoma Study Group Committee of Pediatrics Chinese Anti-Cancer Association. [A collaborative study of children with lymphoblastic non-Hodgkin's lymphoma in China]. Zhonghua Er Ke Za Zhi. 2015 Dec;53(12):931-7. Chinese.

Reference Type: RESULT

PMID: 26887549 (View on PubMed)

Burkhardt B, Woessmann W, Zimmermann M, Kontny U, Vormoor J, Doerffel W, Mann G, Henze G, Niggli F, Ludwig WD, Janssen D, Riehm H, Schrappe M, Reiter A. Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol. 2006 Jan 20;24(3):491-9. doi: 10.1200/JCO.2005.02.2707.

Reference Type: RESULT

PMID: 16421426 (View on PubMed)

Widjajanto PH, Sumadiono S, Purwanto I, Sutaryo S, Veerman AJ. L-asparaginase: long-term results of a randomized trial of the effect of additional 3 doses during consolidation treatment in the Indonesian WK-ALL-2000 protocol. J Pediatr Hematol Oncol. 2013 Nov;35(8):597-602. doi: 10.1097/MPH.0b013e31827e7f89.

Reference Type: RESULT

PMID: 23389497 (View on PubMed)

Yu Q, Wang G, Wang J, Zhang W, Meng L, Cao Y. Primary Testicular and Cutaneous Philadelphia Chromosome Positive B-Cell Lymphoblastic Lymphoma: A Rare Case and Review. Cancer Manag Res. 2022 Apr 21;14:1507-1514. doi: 10.2147/CMAR.S353022. eCollection 2022.

Reference Type: DERIVED

PMID: 35478711 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CCCG-LBL-2016

Identifier Type: -

Identifier Source: org_study_id