Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia

Phase 2

Not yet recruiting

Brief Summary: * Clinical and genetic factors consistent with High risk : Induction → Consolidation

1. BM MRD \< 0.01% : IM #1 → DI #1 → IM #2 → Maintenance

2. BM MRD ≥ 0.01% : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance

3. BM MRD ≥ 0.01% after Consolidation



1. T cell ALL : Change to very high risk regimen

2. Pre-B ALL : IM #1 → Intensification

1. BM MRD \< 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance

2. BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen

* Difference in the number of \'interim maintenance(IM)\' and \'delayed intensification(DI)\' is important for chemotherapies based on MRD.

Detailed Description: * Clinical and genetic factors consistent with High risk : Induction → Consolidation

1. BM MRD \< 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance

2. BM MRD ≥ 0.01% after Induction, \< 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance

3. BM MRD ≥ 0.01% after Consolidation



1. T cell ALL : Change to very high risk regimen

2. Pre-B ALL : IM #1 → Intensification

1. BM MRD \< 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance

2. 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
ALL, High risk with DI #2(Doxorubicin)	ALL, High risk	* Clinical and genetic factors consistent with High risk : Induction → Consolidation 1. BM MRD \< 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance 2. BM MRD ≥ 0.01% after Induction, \< 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance 3. BM MRD ≥ 0.01% after Consolidation <!-- --> 1. T cell ALL : Change to very high risk regimen 2. Pre-B ALL : IM #1 → Intensification 1. BM MRD \< 0.01% after IM #1 : Continue with \'No. 2\' of High risk regimen starting with DI #1 2. 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.

Primary Outcome Measures

Name	Time	Method
Event Free Survival	Up to 5 years	Event-free survival rate for 5 years from the date of registration

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 5 years	The time until defined by date of all-cause mortality from the date of 1st infusion
Recurred rate	Up to 5 years	As the period from enrollment to disease progression/recurrence
Death rate related to infusion	Up to 5 years	The time until defined by date of drug-related mortality from the date of 1st infusion

Locations (5): Seoul National University Hospital
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Seoul, Korea, Republic of
Severance Hospital
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Seoul, Korea, Republic of
Asan Medical Center
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Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
The Catholic University of Korea, Seoul ST. Mary's Hospital
🇰🇷
Seoul, Korea, Republic of