LBL-2016 for Children or Adolescents in China

Lymphoblastic Lymphoma Clinical Trial

Official title:

Modified BFM (Berlin-Frankfurt-Munster)Backbone Therapy for Chinese Children or Adolescents With Newly Diagnosed Lymphoblastic Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02845882
• Other study ID #: CCCG-LBL-2016
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 2016
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Children's Cancer Group, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 2025
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoblastic Lymphoma
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 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
• 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;
• 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;
• 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;
• 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;
• 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;
• 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;

Locations

Country	Name	City	State
China	West China Second University Hospital	Chengdu
China	Shanghai Children's Medical Center	Shanghai

Sponsors (9)

Lead Sponsor	Collaborator
Children's Cancer Group, China	Children's Hospital of Soochow University, Nanjing Children's Hospital, Qilu Hospital of Shandong University, Shanghai Children's Medical Center, Tianjin Medical University Cancer Institute and Hospital, Tongji Hospital, West China Second University Hospital, Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

References & Publications (7)

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 — View Citation

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 — View Citation

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 — View Citation

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 wi — View Citation

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 lymp — View Citation

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. Intens — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival for the whole cohort		3 years
Primary	Event free survival for patients in High risk group		3 years
Secondary	Overall survival for all patients		5 year