RecruitingPhase 3NCT05681260

Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma (T-LBL)

A Randomized Trial Using a Modified COG ABFM Regimen Backbone to Investigate Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma (T-LBL)


Sponsor

Children's Cancer Group, China

Enrollment

200 participants

Start Date

Feb 6, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 12 MonthsMax Age: 18 Years

Inclusion Criteria1

  • Newly diagnosed T-lineage lymphoblastic lymphoma (T-LBL) Stage II-IV

Exclusion Criteria4

  • 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.

Interventions

DRUGPrednisone,Vincristine, Pegylated-asparaginase, Bortezomib,Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine, methotrexate, Dexamethasone, Doxorubicin

Standard 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.

DRUGPrednisone,Vincristine, Pegylated-asparaginase, Bortezomib,Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine, methotrexate, Dexamethasone, Doxorubicin

Standard 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.

DRUGPrednisone,Vincristine, Pegylated-asparaginase, Bortezomib,Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine, methotrexate, Dexamethasone, Doxorubicin, Vindesine, Etoposide, Ifosfamide

High 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.


Locations(2)

Shanghai Children's Medical Center

Shanghai, Shanghai Municipality, China

West China Second University Hospital

Chengdu, China

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NCT05681260


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