CCCG-ALCL-2020 for Chinese Children and Adolescents With Newly Diagnosed High-risk ALCL

Study Overview
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Brief Summary
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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
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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.

Official Title
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Using a Modified ALCL99 Regimen for Chinese Children With Newly Diagnosed High-risk Anapestic Large Cell Lymphoma

Conditions
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Pediatric Anaplastic Large Cell Lymphoma

Intervention / Treatment
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* Drug: P regimen
* Drug: Course A1 + Vin
* Drug: Course B1 +Vin
* Drug: Course A2 + Vin
* Drug: Course B2 +Vin
* Drug: Course A3 + Vin
* Drug: Course B3 +Vin
* Drug: Maintenance therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All enrolled patients stratified into high risk group are assigned to one treatment regimen
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High risk group<br>Stage I, unresected; Stage I with B syndrome Stage II Stage III Stage IV without CNS involvement | Drug: P regimen<br>* 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<br>Drug: Course A1 + Vin<br>* 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;<br>Drug: Course B1 +Vin<br>* 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;<br>Drug: Course A2 + Vin<br>* 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;<br>Drug: Course B2 +Vin<br>* 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;<br>Drug: Course A3 + Vin<br>* 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;<br>Drug: Course B3 +Vin<br>* 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;<br>Drug: Maintenance therapy<br>* Vinorelbine 25 mg/m2 IV, weekly for 3 consecutive weeks followed by 1-week rest. Totally 80 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year event free survival (EFS) | Calculated from the time of diagnosis to the first of the following events: progression, relapse, secondary ,malignancy or death | Up to 3 years | 
| Treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by CTCAEv5.0 | Up to 3years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient compliance | the percentage of patients who complete the maintenance therapy of this modified ALCL99 regimens | Up to 3years | 
| Value of early PET/CT in pediatric ALCL | Prognostic value of early remission of PET/CT after 2 cycles of chemotherapy in pediatric ALCL | Up to 3 years | 
| Value of peripheral blood or bone marrow NPM-ALK or ALK-variants level in pediatric ALCL | Prognostic value of peripheral blood/bone marrow NPM-ALK or ALK-variants level (qPCR) at diagnosis in pediatric ALCL | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anapestic Large Cell Lymphoma, vinorelbine, pediatric, treatment outcome, Chinese