Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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Clinical and genetic factors consistent with High risk : Induction → Consolidation BM MRD &lt; 0.01% : IM #1 → DI #1 → IM #2 → Maintenance BM MRD ≥ 0.01% : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance BM MRD ≥ 0.01% after Consolidation T cell ALL : Change to very high risk regimen Pre-B ALL : IM #1 → Intensification BM MRD &lt; 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen Difference in the number of &#39;interim maintenance(IM)&#39; and &#39;delayed intensification(DI)&#39; is important for chemotherapies based on MRD.

Detailed Description
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Clinical and genetic factors consistent with High risk : Induction → Consolidation BM MRD &lt; 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance BM MRD ≥ 0.01% after Induction, &lt; 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance BM MRD ≥ 0.01% after Consolidation T cell ALL : Change to very high risk regimen Pre-B ALL : IM #1 → Intensification BM MRD &lt; 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen T cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported.

Official Title
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Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia-prospective, Nationwide, Multi-center Study

Conditions
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Pediatric Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: ALL, High risk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: Under 19years of age at diagnosis Patients who are newly diagnosed Pre-B ALL and meet one of the following criteria High-risk group according to the National Cancer Institute (NCI)/Rome: Age greater than or equal to 10 years and less than 19 years at diagnosis, or white blood cell count greater than or equal to 50 x 109/L at diagnosis If extra-bone marrow lesions are identified at the time of diagnosis, Central nervous system involvement (CNS3) or testicular involvement High-risk gene variants: KMT2A rearrangement intrachromosomal amplification of chromosome 21 (iAMP21) If subjects are classified as a standard risk group but have an NGS MRD ≥ 0.01% after remission induction, these subjects will be reclassified and treated as a high-risk group after consolidation. If subjects are under the age of 10 at the time of diagnosis and took steroids for more than 24 hours within two weeks before the diagnosis, the risk group will be determined by the presence of a whole blood test within three days before starting steroids. If a whole blood test is performed within three days before beginning steroids, the risk group will be assessed based on the white blood cell count in the test. If there is no whole blood test before starting steroids, subjects are classified as a high-risk group. If subjects are ten or older at diagnosis, pre-diagnosis steroid treatment will not affect the risk classification. Newly diagnosed T cell ALL Exclusion Criteria: Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia Patients with Down syndrome potential of pregnancy or during pregnancy (patients of childbearing age need adequate contraception for the duration of the trial) Patients who have already received steroid treatment for newly diagnosed ALL specified in the above selection criteria or chemotherapies more than one intrathecal cytarabine treatment Participating in an interventional clinical trial other than this research
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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALL, High risk with DI #2(Doxorubicin)<br>Clinical and genetic factors consistent with High risk : Induction → Consolidation BM MRD &lt; 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance BM MRD ≥ 0.01% after Induction, &lt; 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance BM MRD ≥ 0.01% after Consolidation T cell ALL : Change to very high risk regimen Pre-B ALL : IM #1 → Intensification BM MRD &lt; 0.01% after IM #1 : Continue with &#39;No. 2&#39; of High risk regimen starting with DI #1 BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen T cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported. | Drug: ALL, High risk<br>* Intervention Description : Clinical and genetic factors consistent with High risk : Induction → Consolidation BM MRD &lt; 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance BM MRD ≥ 0.01% after Induction, &lt; 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance BM MRD ≥ 0.01% after Consolidation T cell ALL : Change to very high risk regimen Pre-B ALL : IM #1 → Intensification BM MRD &lt; 0.01% after IM #1 : Continue with &#39;No. 2&#39; of High risk regimen starting with DI #1 BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen T cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The time until defined by date of all-cause mortality from the date of 1st infusion | Up to 5 years | 
| Recurred rate | As the period from enrollment to disease progression/recurrence | Up to 5 years | 
| Death rate related to infusion | The time until defined by date of drug-related mortality from the date of 1st infusion | Up to 5 years | 
| Adverse Event |  | From Day 1 of the clinical trial to 28 days after last drug administration |