Pediatric Anaplastic Large Cell Lymphoma
Conditions
Keywords
Anapestic Large Cell Lymphoma, vinorelbine, pediatric, treatment outcome, Chinese
Brief summary
A prospective study on the efficacy of modified ALCL99 regimens in the treatment of the current Chinese pediatric and adolescent high-risk ALCL and compared with our historical data.
Detailed description
Anaplastic large cell lymphoma (ALCL) accounts for 15% of pediatric and adolescent non-Hodgkin lymphomas (NHLs). In our historical study (retrospective multicenter study), the 3-year event-free survival (EFS) was 65% for 80 eligible patients treated in 10 centers between January 2009 and June 2014. The ALCL99 trial reported a 2-year overall survival of 92% and 2-year event-free survival of 74% then become the current standard frontline treatment for pediatric ALCL. The recent long-term follow-up data from ALCL99 trial highlighted its excellent outcome. A less toxic schedule of methotrexate (MTX) 3g/m2 in a 3-hour infusion without intrathecal therapy reproduced the favorable results from previous reports of NHL-BFM90 protocol with MTX at 1g/m2 in a 3-hour infusion. Additionally, a prospective ALCL-Relapse trial by the European Inter-Group for Childhood Non-Hodgkin Lymphoma demonstrated 80% of patients with a late relapse can be cured by 24 months of vinblastine monotherapy. However, vinblastine would not be advised as a treatment option in mainland China due to its inaccessibility. A pilot experience using single-drug vinorelbine in 4 pediatric patients with relapsed ALCL with satisfactory outcome provides the rational for studying vinorelbine as a front line drug option.
Interventions
DRUGP regimen
Dexamethasone 5 mg/m2 Days 1 and 2; 10mg/m2 Day 3 to 5; Cyclophosphamide 200 mg/m2 Days 1 and 2 Intrathecal therapy Day 1
DRUGCourse A1 + Vin
vinorelbine 25 mg/m2, Day 1 Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Etoposide 100mg/m2, Days 4 to 5; Ifosfamide 800 mg/m2, Days 1 to 5; Cytarabine 150 mg/m2, q12h Days 4 to 5;
DRUGCourse B1 +Vin
vinorelbine 25 mg/m2, Day 1; Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Cyclophosphamide 200 mg/m2, Days 1 to 5; Doxorubicin 25 mg/m2, Days 4 to 5;
DRUGCourse A2 + Vin
vinorelbine 25 mg/m2, Day 1 Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Etoposide 100mg/m2, Days 4 to 5; Ifosfamide 800 mg/m2, Days 1 to 5; Cytarabine 150 mg/m2, q12h Days 4 to 5;
DRUGCourse B2 +Vin
vinorelbine 25 mg/m2, Day 1; Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Cyclophosphamide 200 mg/m2, Days 1 to 5; Doxorubicin 25 mg/m2, Days 4 to 5;
DRUGCourse A3 + Vin
vinorelbine 25 mg/m2, Day 1 Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Etoposide 100mg/m2, Days 4 to 5; Ifosfamide 800 mg/m2, Days 1 to 5; Cytarabine 150 mg/m2, q12h Days 4 to 5;
DRUGCourse B3 +Vin
vinorelbine 25 mg/m2, Day 1; Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Cyclophosphamide 200 mg/m2, Days 1 to 5; Doxorubicin 25 mg/m2, Days 4 to 5;
DRUGMaintenance therapy
Vinorelbine 25 mg/m2 IV, weekly for 3 consecutive weeks followed by 1-week rest. Totally 80 cycles.
Sponsors
Children's Cancer Group, China
Shanghai Children's Medical Center
Nanjing Children's Hospital
Qilu Hospital of Shandong University
Tianjin Cancer Hospital
West China Second University Hospital
Xiangya Hospital
1st Affiliated Hospital of Zhengzhou University
Shenzhen Children's Hospital
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All enrolled patients stratified into high risk group are assigned to one treatment regimen
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* Patient must be ≤ 18 years at the time of diagnosis * Newly diagnosed patients with histologically confirmed high-risk anaplastic large cell lymphoma * No congenital immunodeficiency, HIV infection, or prior organ transplant
Exclusion criteria
* Patients have received prior cytotoxic chemotherapy/target therapy/radiation, if any steroid applied, total prior steroids dosage \> Dexamethasone 40 mg/m2 for the current diagnosis or any cancer * Patients have overwhelming infection, and a life expectancy of \< 2 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-year event free survival (EFS) | Up to 3 years | Calculated from the time of diagnosis to the first of the following events: progression, relapse, secondary ,malignancy or death |
| Treatment-related adverse events | Up to 3years | Number of participants with treatment-related adverse events as assessed by CTCAEv5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient compliance | Up to 3years | the percentage of patients who complete the maintenance therapy of this modified ALCL99 regimens |
| Value of early PET/CT in pediatric ALCL | Up to 3 years | Prognostic value of early remission of PET/CT after 2 cycles of chemotherapy in pediatric ALCL |
| Value of peripheral blood or bone marrow NPM-ALK or ALK-variants level in pediatric ALCL | Up to 3 years | Prognostic value of peripheral blood/bone marrow NPM-ALK or ALK-variants level (qPCR) at diagnosis in pediatric ALCL |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYijin Gao, MD
Shanghai Children's Medical Center
Outcome results
None listed