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

Phase 2

Not yet recruiting

• Conditions: Acute Lymphoblastic Leukemia, Pediatric
• Interventions: Drug: Dasatinib(Sprycel) arm; Drug: Non-Dasatinib(Sprycel) arm

• Registration Number: NCT06257394
• Lead Sponsor: Hyoung Jin Kang

Brief Summary

Very high-risk acute lymphoblastic leukemia

Detailed 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

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-01
• Study First Submitted QC: 2024-02-12
• Last Update Submitted: 2024-02-12
• Study First Posted: 2024-02-14
• Last Update Posted: 2024-02-14
• Study Start: 2024-03-01
• Primary Completion: 2029-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 74

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
[Arm A, Dasatinib(Sprycel) Arm]	Dasatinib(Sprycel) arm	▪ 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.
[Arm B, Non-Dasatinib(Sprycel) Arm]	Non-Dasatinib(Sprycel) arm	▪ 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 Outcome Measures

Name	Time	Method
Event free survival	Up to 5 years

Secondary Outcome Measures

Name	Time	Method
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
Overall survival	Up to 5 years	The time until defined by date of all-cause mortality from the date of 1st infusion