T-cell lymphoblastic lymphoma (T-LBL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in children and adolescents. With current treatment, event-free survival (EFS) rates vary between 75%\~85%. Two different MTX intensification strategies are used commonly: HD-MTX with leucovorin rescue, and Capizzi-style MTX without leucovorin rescue plus PEG-ASP (C-MTX). Although superior outcome of patients with T-ALL receiving C-MTX compared with HD-MTX on the AALL0434 trial, the 2 approaches had not been compared directly in patients with T-LBL. There remains controversy on PET/CT interpretation in children with NHL. Large prospective studies in pediatric patients with T-LBL regarding PET/CT value for this is scarce. Around 1% pediatric patients with T-LBL will not achieve remission at the end of Induction (induction failure). The optimal treatment for this small subgroup is largely unclear. The BFM HR Blocks usually are applied to these patients even though the efficacy is unknown. Novel targeted therapies are needed for use. Dasatinib is identified as a targeted therapy for T-cell ALL in preclinical drug screening.
Newly diagnosed T-lineage lymphoblastic lymphoma (T-LBL) Stage II-IV
Patients with Down syndrome or primary immune comprised disease.
Ph+ T-LBL
Patients must not have received any prior cytotoxic chemotherapy
Any steroids pretreatment for > 5 days in the 7 days or for >14 days in the 28 days before the initiation of Induction chemotherapy. The dose of prednisone or methylprednisone pretreatment does not affect eligibility. Any steroids exposure that occurred > 28 days before the initiation of Induction chemotherapy is allowed. Inhalation and topical steroids are not considered pretreatment. A single dose of vincristine is allowed.
Parallel
Prednisone,Vincristine, Pegylated-asparaginase, Bortezomib,Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine, methotrexate, Dexamethasone, Doxorubicin
DrugStandard risk Arm A: Induction I followed by Consolidation, extracompartmental Capizzi MTX, delayed intensification and 96 weeks' maintenance therapy. Twenty-one or twenty-six triple intrathecal injections for CNS negative or positive patients, respectively.
Prednisone,Vincristine, Pegylated-asparaginase, Bortezomib,Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine, methotrexate, Dexamethasone, Doxorubicin
DrugStandard risk Arm B: Induction I followed by Consolidation, extracompartmental high dose MTX, delayed intensification and 96 weeks' maintenance therapy. Twenty-one or twenty-six triple intrathecal injections for CNS negative or positive patients, respectively.
Prednisone,Vincristine, Pegylated-asparaginase, Bortezomib,Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine, methotrexate, Dexamethasone, Doxorubicin, Vindesine, Etoposide, Ifosfamide
DrugHigh Risk T-LBL: Induction I followed by 2 cycles of BFM HR Blocks, delayed intensification and 96 weeks' maintenance therapy. Twenty-four or twenty-eight triple intrathecal injections for CNS negative or positive patients, respectively.
Event free survival for standard risk patients
To determine the EFS in patients with newly diagnosed standard T-LBL, through randomization, the modified COG ABFM regimen with CMTX to the regimen with HD MTX
Event free survival according to bone marrow MDD
After using the modified COG ABFM regimen, to validate whether bone marrow MDD by Flow at diagnosis is still a prognostic factor for pediatric patients newly diagnosed with T-LBL
Event free survival for high risk patients
To determine the EFS in patients with induction failure who become complete or partial response after using 3 HR BFM Blocks and continue chemotherapy on 3 HR BFM Blocks followed by delayed intensification and maintenance therapy.
Click on the lead sponsor to view all of their trials.
Children's Cancer Group, China
Lead sponsor
Shanghai Children's Medical Center
Collaborator
Beijing Children's Hospital
Collaborator
Children's Hospital of Scow University
Collaborator
West China Second University Hospital
Collaborator
Nanjing Children's Hospital
Collaborator
Qilu Hospital of Shandong University
Collaborator
Tianjin Medical University Cancer Institute and Hospital
Collaborator
Tongji Hospital
Collaborator
Xiangya Hospital of Central South University
Collaborator
The First Affiliated Hospital of Zhengzhou University
Collaborator
Cancer hospital of Shandong Province
Collaborator
Shenzhen Children's Hospital
Collaborator
Wuhan Children's Hospital
Collaborator
The Children's Hospital of Zhejiang University School of Medicine
Collaborator
Shanghai Children's Hospital
Collaborator
Ruijin Hospital
Collaborator
The Second Hospital of Anhui Medical University
Collaborator
Children's Hospital of Hebei Province
Collaborator
Cancer Hospital of Henan Province
Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Collaborator
Qilu Children's Hospital
Collaborator
