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

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.

Conditions

• T-cell Lymphoblastic Lymphoma

Interventions

DRUG

Prednisone,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.

DRUG

Prednisone,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.

DRUG

Prednisone,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.

Sponsors & Collaborators

• Shanghai Children's Medical Center

  collaborator OTHER

• Beijing Children's Hospital

  collaborator OTHER

• Children's Hospital of Scow University

  collaborator UNKNOWN

• West China Second University Hospital

  collaborator OTHER

• Nanjing Children's Hospital

  collaborator OTHER

• Qilu Hospital of Shandong University

  collaborator OTHER

• Tianjin Medical University Cancer Institute and Hospital

  collaborator OTHER

• Tongji Hospital

  collaborator OTHER

• Xiangya Hospital of Central South University

  collaborator OTHER

• The First Affiliated Hospital of Zhengzhou University

  collaborator OTHER

• Cancer hospital of Shandong Province

  collaborator UNKNOWN

• Shenzhen Children's Hospital

  collaborator OTHER_GOV

• Wuhan Children's Hospital

  collaborator OTHER

• Zhejiang University School of Medicine Children's Hospital

  collaborator UNKNOWN

• Shanghai Children's Hospital

  collaborator OTHER

• Ruijin Hospital

  collaborator OTHER

• Second Affiliated Hospital of Anhui Medical University

  collaborator UNKNOWN

• Children's Hospital of Hebei Province

  collaborator OTHER

• Cancer Hospital of Henan Province

  collaborator UNKNOWN

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  collaborator OTHER

• Qilu Children's Hospital

  collaborator UNKNOWN

• Children's Cancer Group, China

  lead NETWORK

Principal Investigators

• Yi-Jin Gao, MD · Shanghai Children's Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-06

Primary Completion

2026-12-31

Completion

2029-12-31

Countries

• China

Study Locations