Treatment of Pediatric Very High-risk Acute Lymphoblastic Leukemia in Korea (VHR ALL)

Hyoung Jin Kang

Status and phase: Enrolling; Phase 2

Conditions: Acute Lymphoblastic Leukemia, Pediatric

Treatments: Drug: Dasatinib(Sprycel) arm; Drug: Non-Dasatinib(Sprycel) arm

Study type: Interventional

Funder types: Other

Identifiers

NCT06257394

H-2401-028-1500

Details and patient eligibility

About

Very high-risk acute lymphoblastic leukemia

Full description

• 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

Enrollment: 74 estimated patients

Sex: All

Ages: 1 to 19 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

[Arm A, Dasatinib(Sprycel) Arm]

Experimental group

Description:

▪ 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.

Treatment:

Drug: Dasatinib(Sprycel) arm

[Arm B, Non-Dasatinib(Sprycel) Arm]

Experimental group

Description:

▪ 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

Treatment:

Drug: Non-Dasatinib(Sprycel) arm