LBL-2016 for Children or Adolescents in China
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Other: 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. |
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
Other Names:
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;
Other Names:
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;
Other Names:
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Other: 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. |
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
Other Names:
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;
Other Names:
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;
Other Names:
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;
Other Names:
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Other: 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. |
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
Other Names:
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;
Other Names:
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;
Other Names:
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;
Other Names:
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;
Other Names:
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;
Other Names:
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Outcome Measures
Primary Outcome Measures
- Event free survival for the whole cohort [3 years]
- Event free survival for patients in High risk group [3 years]
Secondary Outcome Measures
- Overall survival for all patients [5 year]
Eligibility Criteria
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:
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Patients with Down syndrome;
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Morphologically unclassifiable lymphoma
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Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology.
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Evidence of pregnancy or lactation period.
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Ph+ lymphoblastic lymphoma
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | West China Second University Hospital | Chengdu | China | ||
2 | Shanghai Children's Medical Center | Shanghai | China | 200127 |
Sponsors and Collaborators
- Children's Cancer Group, China
- Shanghai Children's Medical Center
- Tongji Hospital
- West China Second University Hospital
- Qilu Hospital of Shandong University
- Tianjin Medical University Cancer Institute and Hospital
- Children's Hospital Of Soochow University
- Nanjing Children's Hospital
- Xiangya Hospital of Central South University
Investigators
- Principal Investigator: Yi-Jin Gao, M.D., Shanghai Children's Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- CCCG-LBL-2016