Treatment of Pediatric Very High-risk Acute Lymphoblastic Leukemia in Korea

* Arm A : Philadelphia chromosome-positive : Induction (Except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.)

* Morphologic Complete Remission after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3

1. If Minimal Residual Disease \& qPCR not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, High Dose Cytarabine → DI(Delayed Intensification) #1 → IM(Interim Maintenance) #2 → DI(Delayed Intensification) #2 → Maintenance
2. If Minimal Residual Disease or qPCR(Quantitative Polymerase Chain Reaction) positivie after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)
* M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)

1. If Minimal Residual Disease \& qPCR(Quantitative Polymerase Chain Reaction) not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, HD Cytarabine
2. If Minimal Residual Disease or qPCR(Quantitative Polymerase Chain Reaction) positivie after the post-reinduction : Consolidation #3 using Blinatumomab

* In Arm A, except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.
* Arm B : Other VHR ALL except Philadelphia chromosome-positive : Induction

* Morphologic Complete Remission after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3

1. If Minimal Residual Disease not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, High Dose Cytarabine → Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)
2. If Minimal Residual Disease positivie after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)
* M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)

1. If Minimal Residual Disease not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, High Dose Cytarabine
2. If Minimal Residual Disease positivie after the post-reinduction : Consolidation #3 using Blinatumomab

• Dasatinib(Sprycel) arm (Drug): ▪ Arm A : Philadelphia chromosome-positive : Induction (Except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.) * Morphologic CR after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3 1. If MRD \& qPCR not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine → DI #1 → IM #2 → DI #2 → Maintenance 2. If MRD or qPCR positive after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT * M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCT 1. If MRD \& qPCR not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine 2. If MRD or qPCR positive after the post-reinduction : Consolidation #3 using Blinatumomab * In Arm A, except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.
• Non-Dasatinib(Sprycel) arm (Drug): ▪ Arm B : Other VHR ALL except Philadelphia chromosome-positive : Induction * Morphologic CR after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3 1. If MRD not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine → Allogeneic HSCT 2. If MRD positive after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT * M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3‡ → Allogeneic HSCT 1. If MRD not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine 2. If MRD positive after the post-reinduction : Consolidation #3 using Blinatumomab

Primary outcomes

• Event free survival [Up to 5 years]

Secondary outcomes

• 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
• Adverse Event [From Day 1 of the clinical trial to 28 days after last drug administration]
• The rate of Hematopoietic stem cell transplantation [Up to 5 years]: The rate of Hematopoietic stem cell transplantation after the Induction and consolidation therapy

Sex: All, ages: 1 Year to 19 Years

Inclusion Criteria:

* Pediatric patients diagnosed with ALL between the ages of 1 and 19 years at the time of diagnosis who meet one or more of the following conditions:

  * Philadelphia chromosome-positive t(9;22)(q34;q11) or
  * Patients with failed remission who had blast > 5% on bone marrow test after initial remission induction therapy or
  * Hypodiploidy (Number of chromosomes \< 44 (less than 44)) or
  * E2A-HLF(Hepatic Leukemia Factor) translocation-positive or
  * When the prognosis is judged to be poor according to NGS-MRD results among high-risk ALL patients (i) In B-ALL, the NGS-MRD(Next Generation Sequencing-Minimal Residual Disease) after consolidation therapy is 0.01% or more, and the NGS-MRD followed during interim maintenance treatment is also 0.01% or more, (ii) In T-ALL, NGS-MRD(Next Generation Sequencing-Minimal Residual Disease) is more than 0.01% after consolidation therapy

Exclusion Criteria:

* Participants with contraindications to medications
* When the study participant or their legal representative withdraws consent
* Pregnant or lactating women (patients of child-bearing potential require adequate contraception during the study period)
* Participants who are medically unsuitable to participate in this study at the discretion of the investigator Participants participating in other interventional studies other than this protocol